10.3: Viruses

Viruses are extremely small—much smaller than bacteria. They can, in fact, infect bacteria. Their basic structure is simply a short strand of RNA or DNA (the viruses’ genes) enclosed in a protein coat. The protein coat allows the virus to enter a cell (as in the example given in Chap. 9 for HIV), much like a key getting you into a house with a matching lock. So it is that a flu virus infects respiratory cells; HIV infects white blood cells; etc.

The protein coat of a virus is unique, enabling us to make a specific antibody to a specific virus. After an infection, we keep making that antibody to protect us against subsequent infections with that same virus. Good for us, not so good for viruses.

The influenza (flu) virus continually alters its protein coat (altering the sequence of bases in its RNA—changing the recipe for its protein coat). If it didn’t, it eventually wouldn’t have anyone but children to infect; others would have developed an immunity from their first encounter with the flu virus (or vaccine).

Scientists track changes in the virus, to provide vaccines in advance of flu season. A different flu shot is offered each year. If the virus hasn’t changed much, antibodies from earlier exposures partially protect us. If there’s a big change, a bigger epidemic is expected, since only a few people, if any, have partial antibody-protection. The severity of symptoms depends on how and how much the virus has changed.

A major change in the virus caused the 1918 flu pandemic (worldwide epidemic) that killed more than 50 million. Many died within hours of the first symptom. Unlike most flu epidemics, about half the deaths were in ages 20-40. Their healthy immune systems worked to their disadvantage, causing a massive immune response with severe consequences, e.g., suffocation from the lungs filling with fluid.

Viruses can’t multiply outside of cells. They don’t even have the ribosomes, etc., to make their own protein coat. They must infect cells to survive. Once inside, they commandeer the cell’s enzymes, transfer RNAs, etc., to duplicate their own genes and make the proteins encoded in their genes.

Remember: the genetic code is universal—GGG “means” the amino acid glycine, whether in a pea, a human, or a virus. Many copies of the virus are made this way, and can go on to infect other cells (the virus can spread).

How can we hamper a virus’s ability to multiply without also hampering the function of our own cells? Because of a virus’s simple structure and the similarity of its molecules to our own, effective treatments are hard to find. There aren’t many chinks in its armor.

In contrast, bacteria are independent single-cell organisms—they multiply all by themselves. They need only nutrients (from dirty dishes, undigested lactose in the colon, candy stuck on teeth, etc.) to survive. They also have cell walls (our cells have cell membranes instead). So, a substance that hampers cell-wall production is devastating for them, but not us.

Penicillin (the first antibiotic discovered) blocks the production of some types of bacterial cell walls and prevents the bacteria from multiplying. The discovery of antibiotics was a medical milestone.*

^{*Alexander Fleming, Ernst Chain, and Howard Florey shared a Nobel Prize in 1945 for discovering penicillin and a way to make useful amounts.}

HIV

HIV (human immunodeficiency virus) carries its genetic material as RNA and has several unusual enzymes, including reverse transcriptase, integrase, and protease. Normally, a cell makes messenger RNA as a matching copy of a section of DNA (normal transcription; Figure 10.3). When HIV infects a cell, DNA is made as a matching copy of HIV’s RNA (reverse transcription).* Cells can’t normally do this, but HIV’s reverse transcriptase enzyme makes it possible.

This “foreign” DNA is then inserted into our DNA. Our cells can’t normally do this either, but HIV’s integrase enzyme makes this possible. Luckily, HIV doesn’t infect sperm and ova, so directions to make the virus can’t be passed to one’s offspring through a parent’s DNA.

HIV infection can proceed in a matter of months or a few years to AIDS (Acquired Immunodeficiency Syndrome), an untreatable death sentence until the advent of antiretroviral therapy (ART) in the mid-1990s. The drugs target HIV’s enzymes, which HIV must have to reproduce.

AZT was the first such drug. It was made as an anticancer drug in 1963, but failed in this use. It was one of hundreds of substances screened in an urgent search for a drug effective against HIV. It works by hampering HIV’s reverse transcriptase enzyme that allows DNA to be made from viral RNA.†

Protease inhibitors target HIV’s protease enzyme that cuts newly made HIV protein into the pieces needed to make more virus. Combining protease inhibitors with drugs that inhibit reverse transcriptase is much more effective and delays drug resistance.

HIV multiplies very fast and produces many mutants, some of them drug-resistant. When resistant forms begin to predominate, drugs lose their effectiveness. There’s less chance of HIV becoming resistant to drug combinations that inhibit more than one of its enzymes. If you’re given a bin of keys, there may be one that locks your house or car, but it’s much harder to find one that locks your house and car. Antiretroviral therapy can enable HIV+ people to live normal lives with normal life expectancy; it also lowers their chance of infecting others.

HIV is mainly transmitted by unprotected vaginal or anal sex, and by the use of contaminated needles. HIV can be transmitted in the womb from mother to child, but is mostly preventable by giving antiviral drugs to HIV+ women during pregnancy. (An infected mother also can pass HIV to her infant through breast milk.)

For all its scariness, HIV is fragile outside the body—more fragile and much harder to get than herpes or hepatitis. A ten-fold dilution of ordinary household bleach (sodium hypochlorite) can destroy HIV in contaminated needles and syringes.

In heterosexual intercourse, women have a much higher risk of infection. A man’s risk goes up if he isn’t circumcised (cells lining the foreskin take in HIV more easily) and/or if the HIV-infected woman has a cervical or vaginal infection (this increases vaginal discharges rich in the white blood cells that can harbor the virus). Prevention is crucial. The infection is curable only by extreme means.

Timothy Ray Brown was the first person to clear the infection. He’d been infected with HIV for 10 years when, in 2006, he came down with leukemia unrelated to his HIV infection. To treat his leukemia, he had a bone marrow/stem cell transplant (preceded by wiping out his own immune system—including his HIV-infected CD4 cells). The transplant donor was selected because of a mutation that made the donor’s CD4 cells highly resistant to HIV infection. The transplant cured Brown’s HIV infection and held off his leukemia. He died of leukemia in 2020 at age 54.

^{*Most viruses can’t do this; those that can are called retroviruses. The first human retrovirus (one that causes a rare leukemia) was discovered in 1978 by Robert Gallo. Francoise Barre-Sinoussi and Luc Montagier shared a Nobel Prize in 2008 for identifying HIV in 1984.
†AZT resembles the DNA-building-block thymidine, so AZT—instead of thymidine—attaches to the DNA being made from viral RNA. This halts the process. AZT lacks the “molecular tail” to which the next DNA-building-block attaches. If DNA were a chain of 100 monkeys, each holding onto a tail, the chain couldn’t be completed if any 1 of the 1st 99 monkeys lacked a tail. AZT is a monkey without a tail. Drugs ddI (dideoxyinosine) and ddC (dideoxycytidine) act similarly.}

COVID-19

COVID-19* is the disease caused by the virus SARS-CoV-2.* We become infected when the Spike protein* on the surface of the virus attaches to cells that have the protein ACE2* on its surface (e.g., cells in our lungs). This allows the virus to enter the cell.

When infected with or vaccinated against a virus, our body makes antibodies (a protein) that protect us from further infection. Without a vaccine, outside sources of antibody can be used. Given intravenuously, the antibodies can help prevent infection in those who are in close contact with infected people, or lessen the effects of early infection by keeping the virus in check.

Convalescent plasma (antibody-containing plasma from blood of people previously infected) has limitations, e.g., availability and purity. In contrast, monoclonal antibodies† made by biotech are purer and can be made in larger amounts.

Soon after being infected with SARS-CoV-2 (before a vaccine was available), then-President Trump, former New Jersey govenor Chris Christie, and then-Housing Secretary Ben Carson, were given an infusion of the monoclonal antibodies before it was available to the general public.

The first two COVID-19 vaccines approved in the U.S. are a novel form—a messenger RNA (mRNA) that holds the recipe for a piece of the spike protein which, in turn, causes the immune response and production of the antibody that protects us from COVID-19 infection. These first two mRNA vaccines were developed by BioNTech/Pfizer and Moderna (combines words modern and rna).

In the face of a pandemic caused by a virus that spreads via the respiratory system, it makes sense to get vaccinated, wear a mask, social distance, and avoid crowds.

^{*COVID-19: Coronavirus Disease 2019 (the year the virus emerged). SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-1 caused the 2003 SARS outbreak). Spike (S) protein that protrudes like a crown (corona) from the surface of coronavirus. ACE2: Angiotensin-Converting Enzyme 2 (membrane protein on cells in our lung, heart, blood vessels, kidneys, etc., that connects with the virus’s Spike protein, allowing the virus to enter our cells).
†Monoclonal antibodies are produced in identical (cloned) cells that make one (mono) specific antibody. Niels Jerne, George Kohler, and Cesar Milstein shared a Nobel Prize in 1984 for discoveries related to monoclonal antibodies.}