In our usual conversations, “having a virus” means being ill with some kind of infection. The virus is what we call the infection itself, (e.g., a cold or the flu) and, at the same time, the little organism that causes the infection. The assumption is that viruses are always and only a bad thing, so the word “virus” is a sort of pseudonym for the illness. Mostly, it’s true that having a virus is not a good thing, but that overlap between the organism itself and the infections caused by viruses mixes up what we know about viruses with what we know about viral diseases. So I will attempt to dispense some information about both subjects, to the best of my abilities.
Viruses are exceedingly small germs – micro-organisms, to use a more specific term. They are individual particles, about one thousand times smaller than the smallest human cells. We commonly think of viruses as harmful, and it is indeed the case that about two hundred types of viruses are known to cause infections leading to illness and in some cases death. It was the emergence of the virus that causes COVID 19, designated SARS-CoV-2, that made almost everyone on Planet Earth wary of viruses.
However, viruses may also act in ways that protect our health. They form part of our organisms’ microbiome – i.e., all the germs that live in our bodies, including bacteria and fungi. All of these play crucial roles in our bodily functions such as digestion, and also contribute to our immunity. Viruses can be harnessed to treat illness, deliver vaccines, and diagnose infections. They are employed as research tools to help us understand biology and disease, and also to develop new drugs. We can thank snippets of viral genomes, incorporated into our DNA tens of millions of years ago, for how our reproductive and nervous systems work.
One specific viral form, the protovirus, is essentially a form of the viral DNA that is integrated into the genome of host cells. It can remain dormant or it can replicate within the host’s DNA without causing the host cell’s death. These viruses have an effect on the reproduction of the host cells; thus they may continue to drive evolution. Protovirus components are thought by some to have contributed to the emergence of life on Planet Earth. From my perspective, this seems unlikely; viruses cannot survive on their own without host cells, so if there were no host cells available, the protoviruses could not reproduce.
A class of specialized viruses called bacteriophages can infect and destroy bacteria. They hijack specific bacteria and employ these bacteria as hosts within which they replicate. These viruses play a key role in regulating microbial populations. They can be employed as therapy against antibiotic-resistant infections and are sometimes used as tools in molecular biology.
The concept of phages as potential treatment options has never overcome initial skepticism. Outside of areas such as Eastern Europe, the medical community discarded the possibility of using phages for treatment of infections when antibiotics emerged in the middle of the twentieth century. Today, however, phage-based therapies are beginning to gain traction.
That’s partly because phages kill bacteria in a different way from antibiotics, offering a potential lifeline as increasing antibiotic resistance plays a role in the deaths of five million people each year worldwide. Phages also offer pinpoint targeting, since most phages evolved to infect one or a few strains of bacteria. Identifying the bacterium causing a patient’s illness and finding a phage that kills it could wipe out the troublemaker and leave beneficial bacteria unharmed.
But viruses can certainly infect humans and make us sick. And viruses can also infect plants, animals, bacteria, and fungi. Each virus infects only specific types of hosts – plant viruses do not infect humans and vice-versa. In humans, viral infections can cause respiratory illnesses, intestinal illnesses resulting in diarrhea and vomiting, sexually transmitted infections, skin conditions, and other ailments.
Viruses are fundamentally different from other microbial organisms in that they cannot reproduce on their own, requiring a host within which to carry out their reproductive process. Essentially, a viral particle is a tiny piece of genetic information encased in a protective coating called a capsid. In order to reproduce, viruses invade the cells of the host – whether in humans or other creatures – and steal the reproductive equipment of the host’s cells. After the virus has reproduced, i.e., made copies of itself, it emerges from the host cell. Unfortunately, after the virus has borrowed the host cell’s reproductive equipment and emerges from the host cell, it leaves the host cell in exceedingly poor shape. That’s basically what constitutes the viral disease – the virus thrives and the host gets sick.
How we learned about viruses
The initial mystery was that more than a century ago, it became evident that infections could be caused by something other than bacteria. Scientists carefully examined the sites of infections and did not find bacteria. They passed fluids from the infection sites through a porcelain filter—the Chamberland-Pasteur filter—that could remove all bacteria visible in the microscope from any liquid sample. But whatever passed through the filter could nonetheless cause disease. That finding led to the discovery of viruses.
Around the end of the 19th century, a Russian botanist – Dmitri Ivanowski – demonstrated that the tobacco mosaic disease could be transmitted from a diseased tobacco plant to a healthy plant by a liquid plant extract, even after that porcelain filter had removed all visible bacteria from plant extract. The obvious assumption was that the disease-causing agent was a liquid, which led to the term “filterable virus,” meaning a harmful liquid that could pass through a very fine filter.
The word “virus” comes directly from Latin. “Virus” means poison, venom, or slimy/poisonous liquid. The word was first used in English around the 14th century for harmful fluids or pus from wounds. In the late 19th century it was used to label fluid infectious agents. Initially, the usual term was “filterable virus.” It was first used in 1898 for the agent that caused the tobacco mosaic disease.
The first virus that caused illness in humans to be identified was the yellow fever virus. In the last years of the 19th century, research by Carlos Finlay, a Cuban physician, demonstrated that mosquitoes were carrying whatever it was that caused yellow fever – presumably an infectious fluid transmitted to humans by mosquito bites. The infectious liquid was later identified as a virus, like the tobacco mosaic disease agent.
By 1928 enough was known about viruses to enable the publication of Filterable Viruses, a collection of essays covering all known viruses. The editor, Thomas Milton Rivers, noted that “Viruses appear to be obligate parasites in the sense that their reproduction is dependent on living cells.” (The term “obligate” as used by Rivers means “of necessity,” meaning that viruses reproduce only as parasites.) Up until the mid-1920s, viruses were mostly thought to be a form of liquid life. The understanding that viruses were independent particles rather than “liquid life” grew gradually during that period.
It was not until the invention of the electron microscope in 1931 that virus particles were shown to have complex structures. The sizes of viruses determined by using this new microscope fitted in well with the sizes estimated by filtration experiments. Viruses were expected to be small, but the range of sizes came as a surprise. Some were only a little smaller than the smallest known bacteria, whereas the smaller viruses were of similar sizes to complex organic molecules. And as we noted above, viruses are about one-thousand times smaller than the smallest human cells. The notion that viruses were particles was not considered unnatural and fitted in nicely with the germ theory.
What are viruses, actually?
A virus consists of a tiny piece of genetic information in a “carrying case” — with a protective coating, as we noted above, which is called a capsid. Viruses do not consist of individual cells, so they do not have all the equipment that cells use to make more copies of themselves. That means that on their own they are unable to reproduce. To do that, they need to invade a cell – human, animal, or plant. The virus carries instructions – genetic material (RNA or DNA) – that enable the virus to use a host cell’s equipment to make more copies of itself,
Some viruses have another protective coating around the capsid. Those without the secondary protective coating are known as “naked viruses.” Viruses can survive outside of a host cell only until their protective coatings break down.
Viruses are grouped in several different classes according to their structures and the diseases they cause. The classification of viruses is somewhat confusing – some are classified according to named families, while others are classified only according to the diseases that they cause. I will probably go into a good deal more detail in this section than is absolutely necessary, but I don’t want to skip over relevant details. I will leave it up to you readers whether to focus or skim.
Influenza viruses (Orthomyxoviridae). This family of viruses includes the influenza A and B viruses. The viruses causing influenza A are designated H1N1 and H3N2. Another class is designated H5N1, and termed “avian flu.” H5N1 is not often transmitted to humans, but when it is transmitted, it is associated with more severe disease and a higher mortality rate. Some influenza A strains can also cause swine flu. The viruses causing influenza B are classified as to lineages named “Victoria” and “Yamagata”and also in groups called “clades” and “subclades.”
Herpes viruses (Herpesviridiae). This very large family of viruses includes more than 130 different members. Nine herpes virus types primarily infect humans, and at least five of these are extremely common in most human population groups. These cause several common diseases such as herpes simplex 1 and 2 (HSV-1 and HSV-2) which can cause oral and genital herpes. Human herpes virus 3 (HHV-3) also known as varicella zoster virus (VZV) is the cause of chicken pox and shingles. However, some cases of herpes are also caused by the Epstein-Barr virus, discussed below.
The Epstein-Barr virus (EBV or HHV-4) has been implicated in several diseases including mononucleosis and some forms of cancer. This virus was the first virus to be classed as an oncovirus owing to its association with many malignant cancers. However, in terms of frequency, the most common threat from Epstein-Barr is infectious mononucleosis; EBV has been identified as the cause of about 90% of the cases of this disease. EBV is also one of the nine viruses that cause herpes in humans. It is one of the most common viruses in humans.
Kaposi’s sarcoma-associated herpes virus (KSHV) is also classified as human herpes virus 8 (HHV -8). Kaposi’s sarcoma is a form of cancer most commonly found in patients with AIDS.
Yet another subtype is human cytomegalovirus (HCVM or HHV-5). Symptoms of infection with this viral class can include fever, fatigue, and sore throat, but these symptoms rarely occur in healthy people. A huge percentage of all adults has been infected with at least one of these viruses, and a latent form of these viruses persists in almost all persons who have been infected. Other herpes virus subtypes are associated with diseases such as roseola and Kaposi’s sarcoma.
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Retroviruses came into widespread attention when it was discovered that the root cause of HIV (human immunodeficiency virus) was a member of a class of viruses termed RNA viruses. These viruses construct their own DNA, and when the virus enters a host organism, it inserts its DNA into the host’s DNA. The retrovirus targets and destroys the host’s CD4+ T lymphocyte cells, which support the host’s immune system. A potential consequence of this action is that the host develops acquired human immunodeficiency syndrome, widely known by its acronym – AIDS. AIDS became notorious about 40 years ago as a disease that was initially thought to be transmitted through sexual contact between gay men, although other common avenues of transmission were quickly identified, such as shared hypodermic needles by drug users.
Another retrovirus is human T-lymphotropic virus 1 (HTLV-1). In most instances, this virus does not cause significant symptoms, but in a small percentage (5% – 10%) of individuals it can bring about conditions ranging in severity from skin rashes and bladder dysfunction to a rare form of leukemia.
Coronaviruses (Coronaviridae, subfamily Orthocoronvirinae). Coronaviruses became notorious only when a virus in that subfamily was demonstrated as the cause of that rapidly spreading and sometimes deadly disease that came to be called COVID 19, short for Coronavirus Disease 2019. In 1965, the common cold (or at least one variety of the common cold) was found to be caused by a member of that viral family. The crown-like appearance of these viruses led to their name. Coronaviruses are RNA viruses, meaning that the virus uses ribonucleic acid (RNA) instead of the more usual DNA. RNA viruses hijack host cells to replicate, resulting in severe damage to the host cells. This can result in diseases like COVID-19, influenza, HIV, Ebola, and measles. These viruses are known for rapid mutation, creating diverse populations that help them adapt and evade immune responses.
Seven distinct coronaviruses can infect humans. The one that causes SARS (severe acute respiratory syndrome), which includes COVID-19, first emerged in southern China in 2002 and quickly spread to 28 other countries. More than 8,000 people were infected by July 2003, and 774 died. A small outbreak in 2004 involved only four more cases. That coronavirus caused fevers, headaches, and respiratory problems such as cough and shortness of breath. As we know, the much greater outbreak of the COVID-19 coronavirus variant started in 2019, resulting in more than seven million deaths worldwide by mid-2024.
MERS (Middle-East Respiratory Syndrome), also caused by a coronavirus variant, emerged in Saudi Arabia in 2012. Almost all of the nearly 2,500 cases have been in people who live in or travel to the Middle East. This coronavirus is less contagious than SARS, but leads to mortality more frequently than in persons who contract SARS. Of the 2,500 known cases of MERS, 858 cases were fatal. MERS has the same respiratory symptoms as SARS, but can also cause kidney failure.
Oncoviruses are the viruses that can cause cancer, named after the Greek word onkos, meaning tumor or mass. Viruses in this class are specifically named only after the diseases that they cause.
Human Papillomavirus (HPV) is a very common, highly contagious sexually transmitted infection caused by over 200 related viruses. Most HPV infections resolve on their own, but some HPV strains can cause genital warts, and cervical, anal, or throat cancers. Human papilloma viruses (HPV) are members of the Papillomaviridae family, which consist of several hundred individual members or “types,” most of which do not cause any significant symptoms, or, in some cases, cause only warts. Some papilloma viruses, such as those labeled papilloma viruses 16 and 18, do have the risk of becoming cancerous. Papilloma viruses have the capacity of infecting all mammals and in some cases other vertebrates such as birds, snakes, turtles. And fish. Fortunately, these viruses have not been found to be transmitted between species.
Hepatitis B / Hepatitis C viruses. These viruses are named after the specific diseases that they cause. Hepatitis B affects about 350 million individuals globally and about 1.2 million in the US, while about 170 million people globally and 2.4 million Americans have hepatitis C. These viruses are the leading cause of cirrhosis of the liver and liver transplants in the US. Hepatitis B and C develop very slowly over a period of several years. Symptoms are minimal, which means that patients are completely unaware of their growing cancers until the disease causes liver failure, requiring transplants. This is an exceedingly difficult procedure, not only because the surgery is highly complex, but because available livers for transplantation are scarce.
Hepatitis viruses are so named specifically because they infect the liver. The different types of hepatitis viruses are identified as hepatitis virus A, B, C, D, and E. In spite of their name, these viruses do not belong to the same genus. Hepatitis A mostly causes a mild illness that resolves without treatment. Hepatitis B can result in more severe illnesses, including some long-term disease. Hepatitis A and B can be prevented through vaccination. Initially Hepatitis C infections may produce no symptoms, so many people with hepatitis C do not know they are infected. As a result, infected persons with hepatitis C are less likely to seek treatment, which can lead to serious liver problems, including liver cancer. There is no vaccine for hepatitis C, but direct-acting antivirals cure more than 95% of hepatitis C infections. The course of treatment is usually eight to twelve weeks. Hepatitis D is uncommon in the US and only occurs in persons who are already infected with hepatitis B. Hepatitis E is rare in the US. That form of hepatitis usually resolves on its own.
Human T-lymphotropic virus type-1 (HTLV-1) is also a retrovirus. As described above, retroviruses insert their own DNA into the host cell’s DNA and essentially kidnap the host cell’s function. HTLV-1 causes a lifelong viral infection, usually without symptoms. However, about 1 in 20 individuals infected with HTLV-1 develop adult T-cell leukemia/lymphoma (ATL), which is a type of cancer. Some persons also develop neurological conditions. It most commonly spreads through sexual contact, breastfeeding, and injected drug use with shared needles.
Enteroviruses (EV) get their name because their transmission route is through the intestinal system – the meaning of “enteric” is “intestinal.” These viruses affect many millions of people on the planet. The most significant disease caused by any member of this class was poliomyelitis. I use the word “was” because polio has largely been eradicated due to the invention of polio vaccines. The first polio vaccine was developed by Dr Jonas Salk in 1955. A second polio vaccine, administered orally, was developed by Dr Albert Sabin and widely introduced in the 1960s. Other members of this class are the Coxsackie A and Coxsackie B viruses. These viruses are principally associated with hand, foot, and mouth disease.
Flaviviruses include West Nile virus, dengue virus, yellow fever virus, and several encephalitis viruses. These viruses are most often spread by mosquitoes and can cause severe illness and death. Flaviviruses increase the severity of their effect by essentially neutralizing the immune responses of their victims. They minimize the host’s immune response by inhibiting the host’s interferon complement, natural killer (NK), B cell and T cell responses.
Orthopoxviruses can cause smallpox, cowpox, mpox (formerly called monkeypox) as well as several other animal diseases. The variant of the virus that causes smallpox, the Variola virus, was eradicated on Planet Earth by 1977 through vaccination with the Vaccinia virus, which was developed by Edward Jenner in 1796. As you probably know, the Vaccinia virus came to be developed based on the realization that exposure to cowpox led to a degree of immunity from smallpox. Milkmaids would get the pox from contact with cows, and observers came to the realization that the cowpox conferred some immunity to the much more serious disease.
Mpox can cause flu-like symptoms in humans as well as an itchy, painful rash. It can spread to humans from several animal species, particularly including monkeys. Some individuals can develop serious illness from this virus, and in some rare instances, mpox can result in mortality, but most people recover with no ill effects.
Other viruses of interest are satellite viruses, which mostly affect plants, and bacteriophages, which specifically infect bacteria. Bacteriophages are currently being investigated as a possible means for the treatment of bacterial infections that do not respond to usual treatment with antibiotics.
In the meantime, a brief bit of fairly good news
The headline in a recent New York Times was “F.D.A. Reverses Decision and Says It Will Review the Moderna Flu Vaccine.” A few weeks ago, Moderna had announced that the FDA had rejected its application for review of its new flu vaccine. The FDA’s reversal certainly does not mean that the new flu vaccine will get the FDA blessing, but at least it means that the door has not been slammed shut.
What is significant about this decision is that Moderna’s flu vaccine is a messenger RNA (mRNA) vaccine. Flu vaccines have been, and will likely continue to be for some time, inactivated bits of the actual flu virus. This has been in line with all vaccines since the earliest vaccines came into existence. The first vaccine, as we mentioned above, was the smallpox vaccine, developed by Edward Jenner. Prior to that innovation, a common practice was to attempt to induce a limited case of smallpox by exposing the individual to a very small amount of the contagious matter in the hopes of bringing about a mild case of the disease and thereby conferring some immunity to that individual. Jenner’s innovation was to inoculate the individual with cowpox, a related disease, which caused a small, mild eruption but did result in complete immunity from the disease. The smallpox vaccine has been sharpened over time, but the general result it that smallpox has been globally eliminated as of 1980.
The vaccines that quelled the COVID 19 epidemic were of a totally new kind. Messenger RNA (mRNA) vaccines consist of a small segment of the virus mRNA which is introduced into the human subject. The subject’s cells can produce the actual viral protein, which is recognized by the subject’s immune system as a foreign invader. In response, the immune system generates specialized proteins called antibodies, which remain in the body after the virus has been eliminated. The result is that the immune system can respond rapidly if the subject is exposed to the same virus again. The antibodies can attach to the virus and mark it for destruction before it causes illness to the subject. The COVID vaccine cannot prevent the virus from entering the human’s body and multiplying, but it alerts the cellular immune system which acts to prevent serious illness.
This class of vaccines is enormously promising. In contrast with non-mRNA vaccines – i.e., all other existing vaccines – mRNA vaccines do not have any infective capacity, which is to say that they do not generate immunity to disease by causing a mild case. Thus, mRNA vaccines can be developed for any type of virus. We can anticipate that, despite opposition from vaccine skeptics, the development of mRNA vaccines will continue and contribute to the control (and potential elimination) of diseases caused by viruses.
I do not need to repeat that the development of such vaccines would be very good news indeed!
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Are there any subjects in the health/medical field that you are curious about? If so, please let me know. In the meantime, several topics have popped up that merit a bit of gumshoeing. These include the relationship of generative AI use with increasing feelings of depression and anxiety, also a number of positive treatment targets for weight-loss drugs, beyond helping people lose weight.
Looking forward to Spring!
Best to all, Michael Jorrin (aka Doc Gumshoe)
