The herpesviruses are a widespread group that infect most of us, and they bring up a number of interesting issues related to viruses. The most striking and consistent feature shared by all the herpesviruses is their ability to persist indefinitely in the host following the initial infection. Once the initial infection subsides, the virus enters a latent period from which at some point the virus can become reactivated, generating transmissible copies.
However, the site in the body where the virus remains in its latent form varies for the different members of this group. With the first three described below, it is in neurons; in the rest, it is lymphocytes or other cells of the immune system. While the majority of infections by these viruses are mild or even asymptomatic, sometimes they can become serious, especially in immunocompromised persons.
The herpes viruses are comprised of double-standed of DNA surrounded by a protein capsid, which in turn is surrounded by a lipid envelope with glycoprotein protrusions.
The herpesviruses infect cells in the usual fashion of viruses: they bind to specific molecules on the surface of the cells, which results in the virus being taken up by the cell. The cells then make multiple copies of the virus, which are released from the cell. Once the immune system has finally controlled the virus, some virus enters a latent period in either neurons or cells of the immune system. While the entire, infective virus itself usually cannot be isolated from these cells, the viral DNA is nonetheless present.
There are eight known forms of herpesviruses, of which we will discuss six here.
Infections by herpes simplex virus type 1 (HSV-1) begins in infancy and by young adulthood at least 50% of people are infected. The initial infection usually does not produce symptoms, although sometimes young children have symptoms such as fever, sore throat and skin or mouth eruptions. Once antibodies are produced, the virus persists only in its latent form, in the cells bodies of neurons in the ganglion of the trigeminal nerve. This serves the face and jaw region. The virus reaches these cell bodies by traveling up the sensory nerves from the site of the original infection. Occasionally, the virus emerges from the latent form, travels down the nerve once again to the mouth and causes herpes labialis, better known as "cold sores". Infections are typically limited to mild discomfort from sores around the mouth, but serious infections causing hospitization do occur. Factors that trigger the reactivation include stress, but others may seem quirky and hard to pin down. Transmission is usually from oral secretions. (HSV-1 sometimes is also the cause of genital herpes, with symptoms much like HSV-2, which is described next.)
Herpes simplex type 2 (HSV-2) is usually the cause of genital herpes and herpes proctitis. Infections begin with the onset of sexual activity, and it is estimated that 25% of adults in the country are infected. However, the majority of individuals are asymptomatic and may be passing along the virus without being aware they have the infection. The normal site of persistence is again neuronal cell bodies, but in this case the location is mainly in the sacral ganglia, which serve the pelvis region. Tranmission of HSV-2 is usually by genital secretions.
Varicella-zoster virus (VZV) is responsible for chickenpox(varicella) and herpes zoster, which is commonly known as shingles. Before introduction of vaccination, almost everyone experienced chickenpox in childhood. Now near universal vaccination against this virus is greatly changing the epidemiology. In chickenpox, the child has an itchy rash composed of vesicles that soon break down to small, shallow ulcers. In adults, the symptoms of chickenpox are usually more severe. Once the chickenpox clears up, the virus persists mainly in the cell bodies of dorsal root ganglia, which are just outside the spinal cord. The virus can reactivate once, causing shingles. This occurs as the virus moves out the nerves associated with the ganglion and causing erythmatous vesicles scattered over the stripe of skin served by the nerves. The most common site is in the middle of the chest or face. It can be quite painful, although the severity varies greatly. The incidence of the reactivation increases with age, with elderly far more likely to suffer a reactivation than the young. Presumably, this is due to a decline in immunocompetence. The virus is spread by the respiratory route for chickenpox or sometimes via infected skin lesions.
The Epstein-Barr virus (EBV) is most commonly associated with infectious mononucleosis and prolonged fever. If the infection occurs in infancy, usually the symptoms are mild. But in developed countries, many people are not infected until later in life. Infections increase during adolescence and perhaps half of those infected at that time have the symptoms of infectious mononucleosis. By middle age, almost all adults are infected.
Epstein-Barr virus is also interesting because it has been proposed so often as a precipitating factor in various disorders. Its role in couple types of cancer is well established. In addition, there is evidence suggesting EBV may play a role in precipitating multiple sclerosis. There have also been speculations that a chronic Epstein-Barr infection is one cause of chronic fatigue syndrome.
Cytomegalovirus (CMV) infects the majority of people in the United States by age 40, but rarely causes symptoms. Occasionally someone shows symptoms similar to mononucleosis caused by EBV. But it is much more of a problem in immunocompromised persons, in which it can cause, for example, infection of the retina or pneumonia. It also is sometimes a problem for a fetus, but only if the mother's first infection happens to occur during the pregnancy.
Human Herpesvirus Type 6 (HHV-6) was found in a recent study in Seattle to infect three-quarters of infants before age 2, with almost all of the infants showing symptoms. Fever and fussiness were the most common symptoms. But HHV-6 is now also known to be the cause of roseola. Infants with this disorder have three to five days of high fever, followed by the sudden appearance of a rose-pink rash typically on the neck and trunk. It turns out to be a major cause of illness in infants brought to emergency rooms due to high fever. Indeed for certain age groups it is as high as 50%. The peak age for infection is about six to nine months. It is spread by contact with oral secretions.
Click here to see images of infections by the different herpesviruses. (You need to be logged in to the UW system to have access to the journal. The picture for HSV-1 is an infection of the nail fold, which is most common among health care workers whose fingers are exposed to saliva in a patient's mouth.)