We’ve covered several human herpesviruses over the past few tutorials, but now it’s
time to dig into the virus that causes mononucleosis, commonly referred to as mono. Epstein-Barr
Virus, or EBV for short, is also known as human herpesvirus 4, and is one of the most
common human viruses out there. Even though it is known to cause mononucleosis, this virus
can cause many other illnesses. It has been associated with Burkitt’s lymphoma, Hodgkin’s
disease, and nasopharyngeal carcinoma, among others.
The virus itself belongs to the subfamily Gammaherpesvirinae, within the human herpesviruses.
Epstein-Barr Virus has a very limited host range. Plus, because the receptor that EBV
binds to, called CD21, is only expressed on certain types of cells, this virus is considered
to have a tissue tropism. CD21 is expressed on B cells of humans and, interestingly, also
New World monkeys, and on some epithelial cells of the oropharynx and nasopharynx. The
trouble is that CD21 is also an important receptor within the innate immune system,
so complications that may arise have slightly higher stakes than other viruses or receptors.
The genome of EBV encodes more than 70 proteins, each responsible for different tasks at different
times during the infection cycle. In a very similar fashion to that of HSV and VZV, EBV
infection goes through a series of highly controlled, complex steps. An intricate system
of different combinations of proteins are expressed at different times to establish
and maintain infection with the virus. Unfortunately, EBV has adapted well to the
human B cell. EBV is able to manipulate the normal B-cell development process to establish
lifelong infection, and promote transmission, to boot. The diseases caused by EBV stem from
one of two things. First, an overactive immune response, like in the case of infectious mononucleosis.
Or second, the lack of effective immune control, like in the case of lymphoma. When B cells
and epithelial cells of the oropharynx are infected with EBV, the virus sheds into saliva,
which makes it pretty easy to spread to other hosts. Infection of B cells and epithelial
cells also helps the virus spread through the blood to other B cells and lymphatic tissue.
One of the ways that the virus creates security for itself is by preventing apoptosis, or
programmed cell death. Because of this, EBV can immortalize B cells. If an individual
experiences the right combination of circumstances, like continued B-cell proliferation along
with several other cofactors, infection could eventually lead to lymphoma.
Okay, let’s scale back for a second and think about the epidemiology of EBV. The virus
is spread very easily through saliva, which could be via kissing, sharing drinks or food,
playing with a toy that another kid just drooled on, or by sharing a toothbrush or eating utensil.
It can also be spread through other bodily fluids during sexual contact, and also by
blood transfusion or organ transplants. When someone first gets infected with EBV, they
can spread the virus for weeks before showing a single symptom. And once the virus is in
your body, it stays there, albeit in a latent, meaning inactive, state. If the virus reactivates,
then you could possibly spread EBV to others even if it was latent for a long, long time.
We also know that more than 90% of EBV-infected people intermittently shed the virus for life,
even when they have no symptoms. Thinking about the age breakdown for this, children
that get infected by EBV typically have very mild symptoms or don’t show any symptoms
at all. The term for this is “subclinical disease.” Moving into adolescents and young
adults, EBV mononucleosis has been called “the kissing disease.” In this age bracket,
disease symptoms can range from basically unnoticeable to severe. It turns out that
at least 70% of the US population gets infected by age 30. Immunosuppressed individuals and
transplant recipients are at higher risk for more serious disease when infected with EBV.
When it comes to prevention, let’s think about this in terms of infectious mononucleosis.
There isn’t an effective treatment or vaccine for EBV infection, and since there’s high
potential for asymptomatic shedding of the virus, it’s pretty difficult to control
the spread of infection. However, exposure to the virus earlier in life is more likely
to prevent the spread of infectious mononucleosis, at the very least. Drinking plenty of fluids,
getting lots of rest, and taking over-the-counter medication can help treat symptoms of mono.
As far as the rest of the human herpesviruses, there are a few more that cause clinically
relevant diseases in humans. Cytomegalovirus, for instance, is a common human pathogen that
infects a small percentage of newborns and about 40% of women that visit clinics for
STIs. Symptoms are typically mild, but this virus is the most common cause of congenital
defects. Human Herpesvirus 8, or HHV8, infects B cells in a similar fashion to EBV, and is
associated with Kaposi’s Sarcoma. HHV8 is typically limited to certain geographic areas,
such as Greece, Italy, and Africa, and is typically limited to patients with AIDS. And
with that, we wrap up our survey of human herpesviruses.