Blog

Epidemiology

What is Epidemiology

Epidemiology is the science that studies the causes and effects of health and disease in a population used in public health to identify risks factors for diseases, and in preventive care to monitor exposure and symptoms and to control the diffusion.

Measures of control based on knowledge of how the virus is transmitted are utilized to limit the spread of the infection. It is important to find the source, or sources of the outbreak and to identify the virus to produce the right weapons to fight and control the transmission and diffusion.

The most used system is the vaccination, and the production of vaccines takes an exceptionally long time to go through the variety of steps of preparation and tests of safety, reliability, and validation; when vaccines are not available, sanitation and disinfection and other measures of control are necessary, in addition to antiviral therapies and immune support.

Infected people are isolated from the rest of the community, and those that have been exposed to the virus are placed in quarantine. Most viral infections of humans and other animals have incubation periods during which the infection causes no signs or symptoms. Incubation periods for viral diseases range from a few days to weeks, during these periods an infected individual or animal is contagious and can infect another person or animal. This too is known for many viral infections, and knowledge of the length of both periods is important in the control of outbreaks. When outbreaks cause an unusually high proportion of cases in a population, community, or region, they are called epidemics. If outbreaks spread worldwide, they are called pandemics.

Viral epidemiology is the branch of medical science that investigates the transmission and control of virus infections in humans. Transmission of viruses can be vertical, as from mother to child, or horizontal, as from person to person. Examples of vertical transmission include hepatitis B virus and HIV, where the baby is born already infected with the virus.

Horizontal transmission is the most common mechanism of spread of viruses in populations and can occur when body fluids are exchanged by saliva, or other secrets, or when contaminated food or water is ingested. It can also occur when aerosols containing viruses are inhaled or by insect vectors, such as when infected mosquitoes penetrate the skin of a host. Most types of viruses are restricted to just one or two of these mechanisms and they are referred to as “respiratory viruses” or “enteric viruses”. The rate or speed of transmission of viral infections depends on factors like the population density, the number of susceptible individuals, as immune-deficient or with chronic disease or any other risk factors, lifestyle, health management, environment, weather and more.

Epidemiologists collect and analyze statistical data to interpret for clinical research purposes and for the monitoring of diseases. The area of study includes the etiology of diseases which is the cause, the origin, the study among people, the transmission, outbreak investigation, surveillance, and more.

Epidemic and Endemic

Epidemic and endemic both analyze mainly the virulence, the modality of transmission and the probability of contaminations.

Endemics are diseases that manifest within a population and which are recurrent, like for example, the malaria in Africa due to the environmental conditions, the vector’s multiplication, the mosquitoes genus Anopheles, and physical condition of population, or HIV among a specific population like heterosexuals and toxic dependents and which originated from a virus present in chimpanzee’.

Epidemics are those that arise periodically and with catastrophic consequences, like influenzas, for example, or infectious diseases like those from staphylococcus, or metabolic diseases like obesity, for example.

Hippocrates, the father of the Medicine was the first scientist to see the relation between diseases and environmental influence, what today is the subject of investigation of the epigenetics, the study of the external causes on genes modification, lifestyle and factors that can influence and modify a genetic pattern and causing mutations of genes that can be turned on and off based on these factors.

The evolution of a species is the result of constant struggle between inherited traits and environmental challenge, and mutations are the adaptation of a trait to survive to the natural selection. Without genetic variation there is not evolution, and some mutations confer advantages to a population to survive adverse conditions while others instead can make more susceptible to a disease. (Peter D’Adamo, Blood Type Diet Encyclopedia)

A way to express the famous laws of Charles Darwin on natural selection, adaptation to the environment and evolution, the foundational principles of Biology.

Epidemiology, as the study of the disease among population along the centuries takes consideration of these important phenomena and reasons why some of these diseases have developed by time based on mutations of species derived from drastic changes of the environment.

Chronology

The chronology of epidemiology begins with the discover of the microbiology.

Around the 16th century scientists started to realize that diseases were caused from alive agents, and that the diffusion and contagious could happen throughout the air, but they still did not know about bacteria and viruses.

A new science developed based on these new founding, the hygiene, as the study of methods and ways to prevent diseases, like disinfectant agents and sterilization techniques, and simple precautions to avoid contagious.

They finally started to figure out that the cause of infections were agents that could be transferred from an individual to another, or a population to another and thanks to the development of the first microscope by Anton Van Leeuwenhoek in 1675 the Germ Theory of disease was born.

Epidemies at those times were frequent and destructive, of course, the knowledge and the tools were still not those we have at present, not vaccines, not antibiotics, or antiviral, or even more norms of modern hygiene and habits of civic populations. The Smallpox, the Black Plague, the Cholera, the Tetanus, and so on, are all diseases almost disappeared thanks to vaccinations.

Louis Pasteur, scientist of the 1800 century, French, chemist, and microbiologist was the founder of the principle of vaccination, the microbial fermentation, and the pasteurization.

His discover was of vital importance at that time and did reduce the mortality of diseases quite common in those periods like, the anthrax, the rabies and puerperal fever. Pasteur is also famous for the discover of the “spontaneous generation” where he was demonstrating with a famous experiment with putrefied meat that nothing can come from nothing, and so that microorganisms could not develop without contamination.

With the new century and advancement of biomedical science, genetic and molecular biology, statistics and epigenetics, new tools of research and analysis and collection of data have changed the spectrum of the study of the epidemiology so as the introduction of variety of conventional and alternatives therapies in addition to the restrictive roles and tools of hygiene have decreased the necessity for vaccinations in many cases.

Epidemiology today is not simply the study of the spreading of diseases mainly as infections through populations in the course of the centuries but has been extended to the analysis of the present diseases, of the diseases of the modern society:  cancer, diabetes, obesity, cardiovascular, neurodegenerative, and genetic.

The factors analyzed in relation to race, gender, and age, are usually fundamental metabolic parameters, and habits, like smoking, alcohol or drugs use, environmental exposure, stressors, chemicals, toxins, etc.

Based on these statistics the most evident correlations are always mainly between lung cancer and smoking, high blood pressure and heart disease, or blood sugar and diabetes, but thanks mainly to the integrative medicine more associations are being evaluated and considered, and for the most connected to the health of the gut microbiome and individual immune resistance.

Epidemics and Pandemics

pandemic is a worldwide epidemic. The 1918 flu pandemic, which lasted until 1919, was a category 5 influenza pandemic caused by an unusually severe and deadly influenza A virus. The victims were often healthy young adults, in contrast to most influenza outbreaks, which predominantly affect, elderly, or otherwise weakened and already debilitated patients. Older estimates were showing that it killed 40–50 million people, while more recent research suggests that it may have killed as many as 100 million people, or 5% of the world’s population in 1918.

Although viral pandemics are rare events, during the 20th century there were four pandemics caused by influenza virus and those that occurred in 1918, 1957 and 1968 were severe.

Several highly lethal viral pathogens are members of the Filoviridae. Filoviruses are filament-like viruses that cause viral hemorrhagic fever and include Ebola virus. Ebola virus disease has also caused intermittent outbreaks with high mortality rates since 1976 when it was first identified. The worst and most recent one is the 2013–2016 West Africa Epidemic.

With the exception of smallpox, most pandemics are caused by newly evolved viruses, these emergent viruses are usually mutants of less harmful viruses that have circulated previously either in humans or other animals.

Severe acute respiratory syndrome, SARS, and Middle East Respiratory Syndrome, MERS, have been caused by new types of coronaviruses. Other coronaviruses are known to cause mild infections in humans, so the virulence and rapid spread of SARS infections—that by July 2003 had caused around 8,000 cases and 800 deaths—was unexpected and most countries were not prepared.

The present coronavirus, SARS Cov-2, originated in bats and responsible of the Covid-19 pandemic emerged in Wuhan, China in November 2019 and has spread rapidly around the world. Unprecedented restrictions in peacetime have been placed on international travel and imposed in several major cities worldwide with lockdown and isolation, public sanitation and regulations, and all reality has change for everyone in this world since then.

Because viruses use vital metabolic pathways within host cells to replicate, they are difficult to eliminate without using drugs that cause toxic effects to host cells in general. The most effective medical approaches to viral diseases are vaccinations to provide immunity to infection, and drugs that selectively interfere with viral replication, but today there are additional variety of alternative therapy suggested mainly to support the immune system, which is the most important tool to fight diseases, and natural compounds capable to contrast the virus multiplication or even the entrance in the host’s cells.

Thanks For Reading.

Mariarosaria M.

Sources:

Epidemiology, Wikipedia

Picture by: Georgia Coastal Health District

More on Viruses

How Three People With HIV Became Virus-Free Without HIV Drugs
Picture by singularityhub.com

Role of Viruses in Human Diseases

Examples of common human diseases caused by viruses include the common cold, influenza, chickenpox to mention some. Many serious diseases such as, AIDS, avian influenza, and SARS are caused by viruses. The ability of viruses to cause disease is called virulence.

Other diseases are under investigation to discover if they have a virus as the causative agent, such as the possible connection between human herpesvirus6, (HHV6) and neurological diseases such as multiple sclerosis and chronic fatigue syndrome. 

Viruses have different mechanisms by which they produce disease in an organism, and which depends largely on the viral species. Mechanisms at the cellular level primarily include cell lysis, the breaking open and subsequent death of the cell. In multicellular organisms, if enough cells die, the whole organism will start to suffer the effects. Although viruses cause disruption of healthy homeostasis, resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the herpes simplex virus, which causes cold sores, to remain in a dormant state within the human body. This is called latency and is a characteristic of the Herpes viruses, including Epstein–Barr virus, which causes glandular fever, and varicella zoster virus, which causes chickenpox and shingles. Most people have been infected with at least one of these types of herpes virus. These latent viruses might sometimes be beneficial, as the presence of the virus can increase immunity against bacterial pathogens, such as Yersinia Pestis.

Some viruses can cause lifelong or chronic infections, where the viruses continue to replicate in the body despite the host’s defense mechanisms. This is common in Hepatitis B virus and Hepatitis C virus infections. People chronically infected are known as carriers, as they serve as reservoirs of infectious virus. In populations with a high proportion of carriers, the disease is said to be endemic.

Host Defense Mechanisms

The body’s first line of defense against viruses is the innate immune system which is made by cells and other mechanisms that defend the host from infection in a non-specific manner. This means that the cells of the innate system recognize and respond to pathogens in a generic way, but it does not confer long-lasting or protective immunity to the host so as the adaptive immune system does.

RNA interference is an important innate defense against viruses, many viruses have a replication strategy that involves double-stranded RNA (dsRNA). When a virus like this infects a cell, it releases its RNA molecule or molecules which immediately bind to a protein complex that cuts the RNA into smaller pieces. A biochemical pathway ensures cell survival by degrading the viral mRNA. Rotaviruses have evolved to avoid this defense mechanism by skipping the uncoating and releasing newly produced mRNA through pores in the particle’s inner capsid. Their genomic dsRNA remains protected inside the core of the virion

When the adaptive immune system of a vertebrate encounters a virus, it produces specific antibodies that bind to the virus and often render it non-infectious. This is called humoral immunity and is performed by two types of antibodies, IgM, which are the first responders and highly effective at neutralizing viruses, but they only last for few weeks, and are the protagonists of the acute infection. The second, called IgG, are produced indefinitely. The presence of IgM in the blood of the host is used to test for acute infection, whereas IgG indicates an infection happened sometime in the past and is indicated as chronic infection.

Antibodies can continue to be an effective defense mechanism even after viruses enter the host cell. A protein called TRIM21, can attach to the antibodies on the surface of the virus particle, this promotes the subsequent destruction of the virus by the enzymes of the cell’s proteosome system.

A second defense of vertebrates against viruses is called cell-mediate immunity and involves immune cells known as T-cells. The body’s cells constantly display short fragments of their proteins on the cell’s surface, and, if a T cell recognizes a suspicious viral fragment there, the host cell is destroyed by ‘killer T’ cells and the virus-specific T-cells proliferate.

Macrophages are specialized cells at the antigen presentation. The production of interferon is an important host defense mechanism. This is a hormone produced by the body when viruses are present. Its role in immunity is complex; it eventually stops the viruses from reproducing by killing the infected cell and its close neighbors.

Not all virus infections produce a protective immune response in this way. HIV evades the immune system by constantly changing the amino acid sequence of the proteins on the surface of the virion. This is known as escape mutation as the viral epitopes escape recognition by the host immune response. These persistent viruses evade immune control by sequestration, blockade of antigen presentation, cytokine resistance, evasion of natural killer cells activities, escape from apoptosis, and antigenic shifts. Other viruses, called neurotropic viruses are disseminated by neural spread where the immune system may be unable to reach them.

Oncoviruses are an established cause of cancer in humans and other species. Viral cancers occur only in a minority of infected people (or animals). Cancer viruses come from a range of virus families, including both RNA and DNA viruses, and so there is no single type of oncovirus (an outdated term originally used for acutely transforming retroviruses). The development of cancer is determined by a variety of factors such as host immunity and mutations in the host. Viruses accepted to cause human cancers include some genotypes of human PapillomavirusHepatitis B, virus, Epstein-Barr.

Prevention and Treatment

Because viruses use vital metabolic pathways within host cells to replicate, they are difficult to eliminate without using drugs that cause toxic effects to host cells in general. The most effective medical approaches to viral diseases are vaccinations to provide immunity to infection, and antiviral drugs that selectively interfere with viral replication.

Vaccination is an inexpensive and effective way of preventing infections by viruses. Vaccines were used to prevent viral infections long before the discovery of the actual viruses. Their use has resulted in a dramatic decline in morbidity or illness and mortality associated with viral infections such as poliomeaslesmumps and rubellaSmallpox infections have been eradicated. Vaccines can consist of live-attenuated or killed viruses, or viral proteins called antigens. Live vaccines contain weakened forms of the virus, which do not cause the disease but, nonetheless, confer immunity, such viruses are called attenuated. Live vaccines can be dangerous when given to people with a weak immunity who are immunocompromised, because in these people, the weakened virus can cause the original disease. Biotechnology and genetic engineering techniques are used to produce subunit vaccines. These vaccines use only the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine. Subunit vaccines are safe for immunocompromised patients because they cannot cause the disease. 

Antiviral drugs are often nucleoside analogues, fake DNA building-blocks, which viruses mistakenly incorporate into their genomes during replication. The life cycle of the virus is then halted because the newly synthesized DNA is inactive. This is because these analogues lack the hydroxyl groups, which, along with phosphorus atoms, link together to form the strong “backbone” of the DNA molecule. This is called DNA chain termination. Examples of nucleoside analogues are acyclovir for Herpes simplex virus infections and lamivudine for HIV and Hepatitis B virus infections. Acyclovir is one of the oldest and most frequently prescribed antiviral drugs. Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called the HIV-1 protease for it to become fully infectious. There is a large class of drugs called protease inhibitors that inactivate this enzyme.

Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease is chronic, and without treatment, they are infected for the remainder of their lives. There is now an effective treatment that uses the nucleoside analogue drug ribavirin combined with interferon. For chronic carriers of the hepatitis B virus has been developed a new treatment that uses a similar strategy with the drug lamivudine.

Thanks for Reading

Mariarosaria M.

Source:

Wikipedia Encyclopedia.

Viruses

Picture by medicalnewstoday.com

Simply continuing the definition of viruses characteristics with the intent of refreshing the basic knowledge. In this chapter are analyzed way they replicate and invade the host cells, life cycle, their genome and classification related, the cytopathic effects, latent and dormant status and host range, to better understand the pathogenicity of the most dangerous as of the present coronavirus.

Replication Cycle

Viruses are acellular units and for this reason do not grow through cell division, instead they use the systems and metabolism of a host cell to produce multiple copies of themselves, then they assemble inside the cell. When infected, the host cell is forced to produce thousands of identical copies of the original virus.

Their life cycle differs between species, but there are six basic stages in their life cycle:

Attachment which is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range and type of host cell of a virus. Attachment to the receptor can induce the viral envelope protein to undergo changes that result in the fusion of viral and cellular membranes.

The attachment is followed by viral entry, virions enter the host cell through receptor-mediated endocytosis or membrane fusion. Plants have a rigid cell wall made of cellulose, and fungi one of chitin, so most viruses can get inside these cells only after breaking the cell wall. Bacteria, like plants, have strong cell walls that a virus must breach to infect the cell; bacterial cell walls are much thinner than plant cell walls due to their smaller size, some viruses have evolved mechanisms that inject their genome into the bacterial cell through the cell wall, while the viral capsid remains outside.

Subsequently to the attachment comes the uncoating. Uncoating is a process in which the viral capsid is removed: this can happen by degradation performed by viral enzymes or host enzymes or by simple dissociation; the result is the releasing of the viral genomic nucleic acid.

Replication of viruses involves primarily multiplication of the genome as synthesis of viral messenger RNA, mRNA, from initial genes, with exceptions for positive sense RNA viruses, viral protein synthesis, possible assembly of viral proteins, then viral genome replication mediated by initial or regulatory protein expression. This may be followed, for complex viruses with larger genomes, by one or more series of mRNA synthesis: late gene expression usually happens with structural or virion proteins.

Then comes the assembly phase where proteins go through modifications. In viruses like HIV, this modification, called maturation, occurs after the virus has been released from the host cell.

Genome replication

During the final step viruses can be released from the host cell by lysis, a process that kills the cell by breaking its membrane and cell wall if present. Some viruses undergo a lysogenic cycle where the viral genome is incorporated by genetic recombination into a specific place in the host’s chromosome. The viral genome is then known as a provirus or, in the case of bacteriophages a prophage. Whenever the host divides, the viral genome is also replicated. The viral genome is mostly silent within the host. At some point, the provirus or prophage may generate active virus, which may lyse the host cells. 

The genetic material of virus particles, and the method of replication of this material varies significantly among different types of viruses.

DNA viruses

The genome replication of most DNA viruses takes place in the cell’s host nucleus. If the cell has the appropriate receptor on its surface, these viruses enter the cell either by direct fusion with the cell membrane or by receptor-mediated endocytosis. Most DNA viruses are totally dependent on the host cell’s DNA and RNA synthesizing and processing devices. Viruses with larger genomes may encode much of these mechanisms themselves. In eukaryotes the viral genome must cross the cell’s nuclear membrane to access this equipment, while in bacteria it is necessary only to enter the cell.

RNA viruses

Replication of RNA viruses usually takes place in the cytoplasm. RNA viruses can be placed into four different groups depending on their modes of replication. The polarity of single-stranded RNA viruses largely determines the replicative mechanism; the other major criteria is whether the genetic material is single-stranded or double-stranded. All RNA viruses use their own RNA replicase enzymes to create copies of their genomes.

Reverse transcribing viruses

Reverse transcribing viruses have ssRNA as RetroviridaeMetaviridaePseudoviridae or dsDNA as Caulimodviridae, and Hepadnaviridae in their particles. Reverse transcribing viruses with RNA genomes as Retroviruses use a DNA intermediate to replicate, while those with DNA genomes, Paretroviruses, use an RNA intermediate during genome replication. Both types use a reverse transcriptase, or RNA-dependent DNA polymerase, to carry out the nucleic acid conversion. Retroviruses integrate the DNA produced by reverse transcription into the host genome as a provirus as a part of the replication process. They are susceptible to antiviral drugs that inhibit the reverse transcriptase enzyme as zidovudine and lamivudine. An example of the first type is HIV, which is a retrovirus, examples of the second type are the Hepadnviridae, which include Hepatitis B virus.

Cytopathic effects on the host cell

These are the range of structural and biochemical effects that viruses have on the host cell. Most virus infections eventually result in the death of the host cell. The causes of death include cell lysis, alterations to the cell’s surface membrane and apoptosis. Often cell death is caused by cessation of its normal activities because of suppression by virus-specific proteins, not all of which are components of the virus particle. Some viruses, such as Epstein-Barr virus, can cause cells to proliferate without causing malignancy, while others, such as Papillomavirus, are established causes of cancer.

Dormant and latent infections

Some viruses cause no apparent changes to the infected cell. Cells in which the virus is latent and inactive show few signs of infection and often function normally. This causes persistent infections, and the virus is often dormant for many months or years; this is what typically happens with the Herpes viruses.

Host range

Viruses are the most abundant biological entities on earth. They infect all types of cellular life including animals, plants, bacteria, and fungi. Different types of viruses can infect only a limited range of hosts and many are species-specific. Some as smallpox virus for example, can infect only humans, and are said to have a narrow host range. Other viruses, such as rabies virus, can infect different species of mammals and are said to have a broad range. The viruses that infect plants are harmless to animals, and most viruses that infect other animals are harmless to humans with the exception of those cause of zoonosis as the rabies virus or the coronavirus to mention some. The host range of certain bacteriophages is limited to a single strain of bacteria and they can be used to trace the source of outbreaks of infections by a method called phage typing. The complete set of viruses in an organism or habitat is called the virome; for example, all human viruses constitute the human virome.

To be continued

Thanks for Reading

Mariarosaria M.

Source

Wikipedia   

https://wordpress.com/refer-a-friend/j2wxElXCm903EzWZ2pRG/

Lactoferrin, Iron Metabolism and Coronavirus

By mivision.com.au

Lactoferrin is a glycoprotein of human secretions and part of the non-specific, or innate immune system, it has been used in trials in Italy on patients affected by Covid-19 as adjunct therapy and seems that has worked pretty well; the patients resolved in the arch of few days and it looks that they are also suggesting as preventive therapy.

The doctor in charge was explaining that the idea of testing lactoferrin came to her while brainstorming on why kids are almost immune to this virus, or if affected in less dramatic forms (other than those with the Kawasaki disease manifestation I would add), and since lactoferrin seems to be a protein under studies of these last periods she started trials on Covid-19 patients and the results were satisfactory.

A review from Italian scientists analyzes the functions and implications of lactoferrin with viral infections and the iron metabolism associate. The article has been published on the “International Journal of Molecular Science” and includes scientists from the University of Rome, Italy, department of Medicine and Infectious Diseases, Tor Vergata, and La Sapienza.

The authors in this review analyze the properties of lactoferrin and its interaction and function with Coronavirus infection and inflammation status, as natural barrier of both respiratory and gastrointestinal route of entry and of inflammation of the virus, and the role of reverting iron disorders caused by the viral colonization.

Under their description iron plays a critical role in the inflammatory processes by facilitating viral progression and exacerbating the inflammatory process at the same time. Iron in excess creates ROS, reactive oxygen species, free radicals which are oxidative and damaging and cause of organs failure among the other degenerative processes.

In pathological conditions the concentration of iron increases and so the susceptibility to infections, ROS production and inflammatory damage. Iron homeostasis includes different proteins like, transferrin, ferritin, and lactoferrin to mention the most common.

During viral infection, the homeostasis of iron is disturbed leading to iron disorders worsened by the action of inflammatory cytokines as interleukine-6, (IL-6), for example.

Studies done on patients affected by viral infections demonstrate that when serum levels of IL-6 increases, the iron saturation of serum levels of transferrin as well as of the receptors decreases; this shows that the host’s status of iron can alter the course of infection and its resolution, in fact significant viral replication requires high iron availability. Clinical data supports that iron homeostasis disorders and dysregulated synthesis brings to intercellular overload of iron which facilitate viral multiplication and spreading of the infection.

Iron imbalance induced by SARS-CoV-2 infection and related inflammatory processes could play a role in the activation and progression of organ impairment. Indeed, the most severe cases of Covid-19, present massive systemic level of infection and inflammatory markers as cytokines and tumor necrosis factor (TNF-a). The excessive release of pro-inflammatory biomarkers referred as “cytokines storm” has evolved as an important system of surveillance to fight infections and inflammations but that may contribute to organ damage and impairment.

Lactoferrin instead could be a key element as adjunct treatment of host defenses acting as protective barrier against the virus. It is already known that lactoferrin plays an important role against microbial and viral infections for its anti-inflammatory effects on mucosal surfaces and that is able to regulate the iron metabolism.

This protein is capable to chelate reversibly two Fe (III), or Fe trivalent per molecule with high affinity, it is a cationic glycoprotein, release iron at pH values lower than 5.5 and can bind trivalent iron until pH values of ~3. It is a protein of the innate immune system which is constitute by lymphocytes T and other type of cells and their products, secrets by exocrine glands and neutrophils during infections and inflammation.

Variety of studies have recognized a highest homology of sequence among human and bovine lactoferrin, ~70% and so of biological functions, for this reason has been applied in studies in vitro and vivo and recognized as “safe” by the Food and Drugs Administration (FDA) and available in large quantities.

By bio-quad.com

The various functions are associate to the capacity to chelate two trivalent iron, or ferric iron, or Fe (III) and to bind to anionic surfaces; with its anti-inflammatory and immunomodulatory properties is capable to control the production of pro-inflammatory cytokines as demonstrated in vitro as in vivo, as in clinical trials.

Several studies describe its antiviral activity towards enveloped and naked viruses of different families, as Retroviridae, Papillomaviridae, Herpesviridae, Adenoviridae, Pneumoviridae, and so on.

It has also been found to obstacle viral entry into host cells by binding competitively to cell surface receptors, mainly negatively charged compounds such as glycosaminoglycans (GAGs).

In general, the antiviral effect of lactoferrin occurs during the initial phase of infection by preventing the viral particle entrance into the host cells, either by blocking cellular receptors than binding viral particles.

For the majority of viruses tested, lactoferrin employs its activity by binding to heparan sulphate, while with few viruses interacting with other surface components.

The results of studies effectuated on mice cells- and which were investigating the role of lactoferrin at the entry of SARS pseudo viruses- revealed that this protein blocks the entry by binding to the spike protein of the virus, showing this way that its inhibitory activity takes place at the attachment viral stage.

The present accepted model suggests that lactoferrin could block viral entry by interacting with heparan sulfate proteoglycans, which mediate the transport of extracellular virus particles from the low affinity sites to the high affinity specific entry as ACE-2.

These results suggest that lactoferrin could play a protective role in host defense against SARS-CoV-2 and host cells. The ability to enter inside the nucleus may also reduce the activation of the cytokines storm avoiding systemic, lung, or intestinal iron homeostasis disorders as well as diseases exacerbation.

Recently have been also investigated the effects of lactoferrin in regulating the activation of plasminogen, to verify if this molecule is involved in controlling the coagulation cascade promoted by the coronavirus.

Current studies have shown that can exercise negative regulatory effects on cells migration via inhibition of prostaglandins activation and through the regulation of fibrinolysis. This activity has been also confirmed by evidence of a peptide with the amino acids sequence derived from lactoferrin showing antithrombotic activity.

The authors test that there are more than 140 trials available on trials.gov, among these, major contribution of lactoferrin has been demonstrated on anemia, bacterial and viral infection, in both communitarian and nosocomial inflammation and prevention of sepsis. These trials assess the safety, tolerability, and efficacy of lactoferrin as oral dietary supplements and/or as intranasal spray.  

It seems an alternative and adjuvant therapy to take in consideration since already applied in Italy and proved to function, eventually to add among the other alternative and validated therapies to the regular and current most utilized and verified therapies for Covid-19 in hospital and at home, for those who does not require hospitalization.

The data in this article have been summarized and rearranged from the original article written from Italian scientists with the exception of some of my personal comments and observations.

Thanks For Reading

Mariarosaria M.

References:

“Lactoferrin as Protective Natural Barrier of Respiratory and Intestinal Mucosa against Coronavirus Infection and Inflammation” International Journal of Molecular Medicine

Int. J. Mol. Sci. 2020

http://www.mdpi.com/journal/ijms

Biology of Viruses

By FuseSchool, youtube.com

Life properties

Viruses have been described as “organisms at the edge of life”, since they resemble living organisms, they possess genes, evolve by natural selection, and reproduce by creating multiple copies of themselves through self-assembly.

Although they have genes, they do not have a cellular structure, do not have their own metabolism, and require a host cell to make new products. 

Viruses are found wherever there is life and have probably existed since living cells first evolved. The origin of viruses is unclear because they do not form fossils, molecular techniques are used to investigate how they developed. 

Origins

There are three main hypotheses to explain the origins of viruses:

Regressive hypothesis

For this theory viruses could be small cells that parasitized larger cells, genes not required by their parasitism were lost with time.

Cellular origin hypothesis

The cellular hypothesis suggests that some viruses may have evolved from bits of DNA or RNA that “escaped” from the genes of a larger organism. The escaped DNA could have come from plasmids or transposons.

Co-evolution hypothesis

This theory proposes that viruses may have evolved from complex molecules of protein and nucleic acid at the same time that cells first appeared on Earth and would have been dependent on cellular life for billions of years.

Viroids are molecules of RNA that are not classified as viruses because they lack a protein coat. They have characteristics that are common to several viruses and are often called subviral agents. Viroid are important pathogens of plants. They do not code for proteins but interact with the host cell and use the host genetic material for their replication. 

The Hepatitis delta virus of humans has an RNA genome similar to viroid but has a protein coat derived from hepatitis B virus and cannot produce one of its own. It is, therefore, a defective virus. These viruses, which are dependent on the presence of other virus species in the host cell, are called satellites and may represent evolutionary intermediates of viroid and viruses.

The evidence of an ancestral world of RNA cells and computer analysis of viral and host DNA sequences are giving a better understanding of the evolutionary relationships between different viruses and may help identify the ancestors of modern viruses.

Structure and Morphology

A complete virus particle, o virion, consists of nucleic acid surrounded by a protective coat of protein called capsid. These are formed from identical protein subunits called capsomeres. Viruses can have a lipid “envelope” derived from the host cell membrane. The capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological distinction.

Complex viruses code for proteins that assist in the construction of their capsid. Proteins associated with nucleic acid are known as nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid.

Based on the shape of the capsomer there are different types:

Helical, as for the tobacco mosaic virus, Icosahedral as for the rotavirus, Prolate, as for the head of bacteriophages.

Some species of virus envelop themselves in a modified form of one of the cell membranes with an outer lipid bilayer known as a viral envelope, the lipid membrane itself originate entirely from the host. The influenza virus and HIV use this strategy. Most enveloped viruses are dependent on the envelope for their infectivity.

Complex viruses possess a capsid that is neither purely helical nor purely icosahedral, and that may possess extra structures such as protein tails or a complex outer wall. Some bacteriophages have a complex structure consisting of an icosahedral head bound to a helical tail, which may have a hexagonal base plate with protruding protein tail fibers. This tail structure acts like a molecular syringe, attaching to the bacterial host and then injecting the viral genome into the cell.

Genome

By studyblue.com

Viruses contain more structural genomic diversity than other living organisms and microorganisms. There are millions of different types of viruses.

A virus has either a DNA or an RNA genome and is called DNA virus or RNA virus, respectively. The vast majority of viruses have RNA genomes. Plant viruses tend to have single-stranded RNA genomes and bacteriophages tend to have double-stranded DNA genomes.

Viral genomes are circular, as in the polyomaviruses, or linear, as in the adenoviruses.  In RNA viruses and certain DNA viruses, the genome is often divided into separate parts, and is called segmented. For RNA viruses, each segment often codes for only one protein and they are usually found together in one capsid. All segments are not required to be in the same virion for the virus to be infectious.

A viral genome, irrespective of nucleic acid type, is almost always either single-stranded or double-stranded. Single-stranded genomes consist of an unpaired nucleic acid, double-stranded genomes consist of two complementary paired nucleic acids. The virus particles of some virus families contain a genome that is partially double-stranded and partially single-stranded.

For most viruses with RNA genomes and some with single-stranded DNA genomes, the single strands are said to be either positive sense or negative sense, depending on if they are complementary to the viral RNA messenger, m-RNA.

Negative-sense viral RNA is complementary to m-RNA and thus must be converted to positive-sense RNA by an RNA-dependent-RNA-polymerase before translation.

In general, RNA viruses have smaller genome sizes than DNA viruses because of a higher error-rate when replicating and have a maximum upper size limit, errors during replication make the virus useless or uncompetitive. To compensate, RNA viruses often have segmented genomes reducing this way the chance that an error in a single-component genome will incapacitate the entire genome.

In contrast, DNA viruses generally have larger genomes because of the high fidelity of their replication enzymes. Single-strand DNA viruses are an exception to this rule, as mutation rates for these genomes can approach the extreme of the ss-RNA virus case.

Genetic mutation

By kiputsc.wordpress.com

Antigenic shift, or reassortment, can result in novel and highly pathogenic strains of human flu. Viruses undergo genetic change by several mechanisms. These include a process called antigenic shift where individual bases in the DNA or RNA mutate to other bases. Most of these point mutations are “silent”—they do not change the protein that the gene encodes—but others can confer evolutionary advantages such as resistance to antiviral drugs.

Antigenic Shift occurs when there is a major change in the genome of the virus. This can be a result of recombination or reassortment. When this happens with influenza viruses, pandemic might result. RNA viruses often exist as swarms of viruses of the same species but with slightly different genome nucleoside sequences. Such species are a prime target for natural selection.

Segmented genomes confer evolutionary advantages; different strains of a virus with a segmented genome can shuffle and combine genes and produce progeny viruses or offspring that have unique characteristics. This is called reassortment or ‘viral sex’.

Genetic Recombination is the process by which a strand of DNA is broken and then joined to the end of a different DNA molecule. This can occur when viruses infect cells simultaneously. Recombination is common to both RNA and DNA viruses.

Thanks For Reading

Mariarosaria M.

Source: Wikipedia: Virus