Viruses are tiny, tiny particles that are not visible by anything but the electron microscope. They are referred to as obligatory intracellular parasites because they can survive only by replicating and getting energy inside the cells of their hosts. They are only around 20 or 30 nanometers in size.
They’re extremely simple. They are composed of an outer protein coat and an inside with free strands of RNA or DNA; there are two kinds of viruses. There’s no nucleus, there’s no metabolic machinery, there are no lipids and no proteins—nothing but the ability to replicate and information required on how to get into a cell.
Viruses are made of a complicated outer coat and coils of some kind of nucleic acid, either RNA or DNA, and it might look on cross-section something like this. There’s no substrate for it to use; it has to use everything that the cell provides for its replication, and it can live outside the host for a very variable period of time, but it has to get in and hijack the metabolic machinery of the cell. Usually the cell is going to die in the process, but not always; sometimes it can become dormant.
It generally resists phagocytosis because these particles are just too small to be attacked by the bigger cells. It elicits an immune response more than an inflammatory response which may result in the production of lethal antibodies and a very strong immune memory. Once you’re infected, you may get some antibodies that can kill the virus and then long-term memory through the memory cells, since most of these are attacked by the humoral or the antibody part of the immune system. It’s not so much a cellular response but a molecular response.
Getting into Your Cells
Viruses have receptors that attach to a specific cell and then cause penetration where it is absorbed in through the cell membrane and into the cytoplasm. The RNA viruses generally replicate inside the cytoplasm and make messenger RNA, which then translates the DNA and uses DNA to make new virus particles. A DNA virus usually gets into the nucleus, uses the host DNA directly, and makes copies of its own DNA and uses the machinery of the cell to make new protein coats. It goes out by budding and gets back into the environment. We’re usually talking about hundreds or thousands of progeny—the viruses, of course, are only a thousandth the size of the cell, so they’re much smaller—in contrast to a bacterium, which produces only two copies for every one that it starts with. We’re talking about exponential growth here. Sometimes the viruses will immediately enter a new cycle; other times they’ll go dormant and wait for certain signals to replicate.
In general, viruses should never be treated with antibiotics; they are not effective.
A viral infection has a wide range of what it can do to the cell. It may damage the protein synthesis so that the cell is weakened or dead. It can interfere with the immune recognition system. Sometimes it can cause the host to attack the cell and kill it as if it were a foreign cell. It can malignantly transform. Sometimes there’s so much cell damage that you have that perfect milieu for bacterial replication, and you have a bacterial super-infection. It’s an infection superimposed on the virus. In the good practice of medicine, this is when we usually jump in with antibiotics. In general, viruses should never be treated with antibiotics; they are not effective. In fact, we have no antiviral medicines that can be widely used.
The Power of Vaccination
Vaccination is our main protection against viral illnesses, so prevention and the degree of immunity are very variable. A common cold virus just doesn’t stimulate a big immune response, whereas something like polio or mumps can give you virtually lifelong protection through the memory cells. The key problem with the virus is that it multiplies in a vast exponential mode so that its numbers are huge; therefore, random mutations are going to be huge, and very likely over a period of time, natural selection is going to select for the best and the most resistant virus that may evade our natural or acquired resistance or any treatment we might try to use. There’s something called mutational drift—the constant, slow change that a mutation will cause in these viruses. Yet there are other viruses that stay very stable and don’t form many types of subspecies.
Diagnosing Viral Illness
The diagnosis of a viral illness is usually clinical; we usually see the signs and symptoms of a particular disease. Other times, we have to use immunologic techniques. For example, West Nile fever can be diagnosed through monoclonal antibodies. We use cultures for bacteria—we just swab or have you cough onto a plate of nutrient agar or jelly. This is very cheap, very quick, and easy to do. Viruses have to grow on cells. They can’t grow on gel, and so viral cultures are very difficult and very expensive; we don’t use them very often. We try to use antibody immune response or just a symptom complex to tell whether the patient has a specific disease.
Endemic, Epidemic, or Pandemic?
There are three terms that we need to define: endemic, epidemic, and pandemic. Endemic is something like the common cold. It means a constant low level of prevalence within a certain community or geographic area without big spikes. Epidemic is that big spike where lots of people get sick at once within a certain area or population. Pandemic is an epidemic that becomes worldwide, and pandemic is what we’re most concerned about these days. We’ll start with the influenza pandemic that started in 1918. It was called the Spanish flu, which had more to do with the animal origin than the geography. It killed somewhere between 50 and 100 million people worldwide. It was a huge, terrible, terrible pandemic. The plague, as you remember, killed about 25%–30% of Europe. This was a pretty bad one, but it went all around the world. What’s amazing is that researchers have reconstituted the 1918 flu today. They have taken cells from people who died of flu, the remains of people who died of flu over 100 years ago—some Inuits in Alaska and some soldiers that they knew of—and gotten the DNA of these viruses from these patients. There are only eight genes here, so it’s not a big genome to replicate. But they have replicated it and created a new virus with it. It’s a virus that is effective and can do just what that 1918 flu could do.
Inside Avian Flu
The 1918 flu and bird flu are very special. The normal influenza that we are used to talking about—we get our flu shots every year—is a very superficial infection. They don’t go very deep into the lungs. They’re not what we call virulent and they tend to have a mortality associated with old age or debility with the very, very young. In the middle, most people get over the normal, run-of-the-mill, garden-variety flu. The 1918 flu and avian flu that we’re seeing today are much deeper. They go way deeper in the lungs. They cause what we think is a cytokine storm. It elicits a viscous cycle of the cytokines we talked about in the immune system, which won’t turn off, and kills cells and causes huge damage—hemorrhage and inflammation in the lungs.
There are a couple of terms we need to talk about. First, the term H and N, the type of flu: H stands for hemagglutinin gene. Hemagglutinin is a test you do to see if red cells can be clumped together. But this gene in this bird enables the virus to penetrate the cell. It’s the key to the lock in getting in the cell. That’s the H number. The N number stands for neuraminidase gene and it’s the way out. It allows the virus particle to get out; it’s the scissors that cuts away the final ties to the cell. The flus are numbered in the sequence of their discovery, so we call the 1918 flu, for example, H1N1. The modern flu that we’re looking at now, the avian flu, is called H5N1. We think this variant may be every bit as deadly as the 1918 flu, but it has one major difference. This flu, if you look at the pattern of the worldwide transmission, these lines showing the roots of the spread are actually not human migration roots; they’re bird migration roots. Because, right now, this flu is going from birds to people and has not made that jump that the pandemic of 1918 made in going from people to people. In other words, we don’t get that aerosol infection. This is the horror that we’re waiting for because, if you notice, the pandemic flu has basically been spreading up and down in the same area. It hasn’t crossed the oceans yet as far as we know. But what we’re horribly worried about is that this flu, if it goes respiratory from human to human, may make the 1918 flu look like child’s play because of modern transportation and a slightly long enough incubation period when a patient is asymptomatic. A patient has to have time to let this virus develop before it causes symptoms, but the patient is contagious. So, as you know, patients can get on an airplane with just a mild cough and then because of the closed ventilation systems infect everybody on that airplane. They get out at the next port and, again, you have exponential transmission, the likes of which we never saw in 1918 because we didn’t have this kind of travel. Epidemiologists and people concerned with preventive medicine are terrified of the time when this flu might go human to human. This avian flu is one of our great fears.
Measles, SARS, and the Respiratory Viruses
Let’s talk about some of the other respiratory viruses, which include measles and SARS, which we heard about not long ago, Severe Acute Respiratory Syndrome. It sounds like a generic term, but it was a specific virus. Influenza we see on a yearly basis and it has quite a mutational drift. That’s why we need a new shot all the time, we’re always trying to keep ahead of that. Measles is a virus and there are about 30 million cases a year with 800,000 deaths. This is a huge number of deaths, mostly in the poorer countries where they don’t have widespread vaccination. It’s completely vaccine-preventable with lifelong immunity. It is respiratory droplet transmission, but it affects the lymphatic cells. It can live and replicate in monocytes, in T cells, in macrophages. That’s very bad for the host because those cells eventually get into the bloodstream and then the virus can spread hematogenously, get a ride through the bloodstream, and you get the rash, an allergic reaction, which is the reaction of antibodies and antigens in the skin. Cough, pneumonia—you can get encephalitis, brain swelling, which can kill you; you can get hepatitis and a whole range of diseases. To diagnose measles, you don’t have to draw blood. If you look in the roof of a patient’s mouth and see little white spots on the palate and then the patient has the rash, that’s measles. Those are called Koplik’s spots; we don’t see them with anything else. It’s an easy diagnosis and a very difficult disease.
The Fall of Polio
The enteroviruses are the viruses that are passed on through the GI tract. They include polio, mumps, and hepatitis A, B, C, D, and E. They include many of the infantile diarrheas and Norwalk virus—the cruise ship virus that’s very contagious. The three main strains of polio infection have remained constant. They’re RNA virus and they’re fecal-oral transmission, and it’s been an interesting history. It was once very prevalent in the upper socioeconomic levels of society. The reason was that the wealthier families kept their children very well protected from this virus—hand washing, cleaner surroundings, and less crowding. Polio virus is not very serious in the very young and in infants. It’s a bad cold and a fever and a cough and then they get over it. Now the transmission is the fecal-oral route. It passes through the mouth, it comes out in the feces, and we all know, as we watch our children and grandchildren play, that the hands go in the mouth and we’re horrified by what they’re putting in their mouth. These babies in crowded conditions and with lots of siblings passed that virus through their family when they were very young. They got sick, they got immunity, and they got over it. The upper levels of society at that time kept their children clean and isolated during the time of the outbreaks, and they never got immunity until they got to be older or even adults. That’s when the virus is very, very serious and they got paralytic polio.
Nowadays, the upper socioeconomic classes and the first-world countries have all their population vaccinated and they’re protected. This is now a disease that’s almost eradicated and we’re trying to do that with massive inoculations in the third world, which is where the final remnants are. Like smallpox, it should be totally eradicable with the willpower and funding to do it. This is one of those examples where what we used to call “Vitamin D,” or dirt, is good for you to a certain extent. It’s good to let the children get exposed in their preschools to lots of various germs, as long as they don’t get too sick, so they can develop antibodies; polio was the classic case. It infects only humans. Since there are no animal reservoirs, so we should be able to get rid of polio.
The original Salk vaccine was a killed vaccine given by injection. In the 1950s, when the vaccine started to become widely used and the patients were protected from polio, it really seemed like a miracle.
The original Salk vaccine was a killed vaccine given by injection. In the 1950s, when the vaccine started to become widely used and the patients were protected from polio, it really seemed like a miracle. Then the Sabin vaccine came in. That was a live vaccine, and it gave not only protection, but it also prevented the carrier state and it gave patient-to-patient immunity because you could vaccinate somebody in the family and the children could pass the immunity along to each other and to others. In a day care center, everybody might get protection from polio if one child were protected.
The Modern Plagues
I want to move on to something I call the modern-day plagues. These are viruses that are emerging now. They have been extremely frightening and we don’t know a lot about them, especially their origins. And these are called arboreal, meaning tree or forest, hemorrhagic fevers. These diseases cause very, very high fever and massive bleeding from almost every orifice in the body. The big ones are Ebola and Marburg, and there’s Lassa fever, which is related, and dengue fever, which we’ve known about for a long time.
The big one that emerged in 1976 was Ebola virus. It’s called a Filovirus because it’s long and threadlike, highly contagious from secretions and blood. So it’s passed by external contact. It has a nonhuman reservoir in monkeys and chimps and originated in Africa. It’s an RNA virus. We don’t know of any carriers; nobody seems to survive this virus to carry it. It has only the acute infectious disease states. The important thing in its prevention of spread has been that fortunately, or unfortunately for the victim, it’s not a very long illness, without a long, contagious incubation period. These patients aren’t getting on airplanes or sitting around airports or crowded places, they are too sick. They’re bleeding from every pore of their body and they die rather quickly. We don’t have a specific vaccine for this yet; we’re experimenting with virus-like particles. We just use mechanical separation and isolation, the extreme levels of physical protection, and we hope that we can contain it purely by containing the geography of this disease.
The other one, which was discovered in 1967, is called the Marburg virus. The virus looks like a shepherd’s crook. It has a little knob at the end of it, kind of a funny shape. It’s very similar to Ebola, it’s an RNA virus and the four species of Ebola and the one of Marburg are the only known members of the Filoviridae family. So this is a small group we’re just learning about. The outbreak of this virus occurred in Marburg, Germany, and in Frankfurt. Workers were doing research on the African green monkey, using their tissues. It’s indigenous to Africa, specifically to Uganda, western Kenya, Zimbabwe, the center core of Africa. The host reservoir is not known. It’s a close-contact transmission, again, with exchange of fluids, direct contact, or equipment infected with the virus or blood or serum from a patient. Very bad fever, chills, and headache, and these people really do die a horrible death. We have nothing we can do but support them. They get pancreatitis, liver failure, and multi-organ failure, and they almost invariably die. Right now we just have to find a way to contain it, although many laboratories are at work trying to find a vaccine.