Epstein-Barr virus (Infectious mononucleosis)

Definitions & Key takeaways

Epstein-Barr virus (EBV) also known as human herpesvirus-4, is an enveloped double-stranded DNA virus of the Herpesviridae family, commonly known to be the cause of infectious mononucleosis (IM). It is also associated with other diseases such as Burkitt's lymphoma, Hodgkin's disease, and gastric carcinoma. Most people are infected with EBV at some point in their lives. In most cases, the virus produces no symptoms and goes away on its own. However, in some people, EBV can cause serious health problems. People with IM present with fever, sore throat, swollen lymph nodes, and liver problems.

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The Epstein-Barr virus, or EBV, also known as human herpesvirus-4, or HHV-4, is an enveloped virus of the Herpesviridae family, which contains linear, double-stranded DNA.It is the most common cause of infectious mononucleosis, more commonly known as “mono.” EBV infection begins when saliva or respiratory secretions that contain the virus from one person make their way into someone else’s mouth.
Often, this happens by sharing food or drinks, or by kissing, which is why mono is sometimes called the “kissing disease” and why it is most common in adolescents and young adults, aged 15-24, because young people are often doing the smooching.
When EBV reaches the new person’s mouth, it infects two types of cells in the oropharynx: epithelial cells, which line the surfaces of the oropharynx, and B cells, which are lymphocytes, or lymphoid cells, that create antibodies to fight off infections.
In the epithelial cells, the virus undergoes the lytic cycle, whereby its DNA gets transcribed and translated by cellular enzymes, which help to form viral proteins, which are packaged into new viruses, which can leave the host cell destroyed, or lysed, and subsequently infect neighboring epithelial cells.
The viruses that reach the lymphoid tissue of the oropharynx, the tonsils, infect their main target, B cells, by attaching to their CD21 receptor, also known as the CR2 receptor.
The infected B cells then enter the latent phase, in which the virus just sort of hangs out in the host cell instead of killing it.
They then carry and spread the infection along their normal trajectory to the other lymphoid tissues of the body, including the liver, spleen, and lymph nodes.
The body’s immune system reacts to the infection by mounting a humoral response, whereby the B cells create antibodies to fight off the virus, and a cellular response, in which cytotoxic (or CD8+) T cells, which are lymphocytes that mature in the thymus, work to kill the infected B cells.
This limits their ability to continue to spread the virus throughout the lymphoid tissues, thus stopping the infection from spreading.
Now, in most EBV-infected individuals, the infection is controlled, and, as a result, most people do not develop symptoms.
When someone infected with EBV does develop symptoms, that’s called infectious mononucleosis or mono. The most common symptoms are fever, pharyngitis, or inflammation of the throat, and lymphadenopathy, or swollen lymph nodes.
The inflammation of the throat makes sense since the epithelial cells are infected, and swollen lymph nodes makes sense since infected B cells spread throughout the lymph tissue of the body, causing it to swell up.
The lymph nodes that are most commonly swollen as a result of an EBV infection are the posterior cervical lymph nodes in the back of the neck, because those lymph nodes drain the tonsils where the B cells are initially infected.
Another very common symptom of mono is fatigue, or extreme tiredness, which can be particularly severe in mono and can last for several months.
Other possible symptoms include tonsillitis, or inflammation of the tonsils, palatal petechiae, or red spots on the palate, hepatomegaly, or an enlarged liver, and splenomegaly, or an enlarged spleen.
The tonsillitis may be exudative or non-exudative, meaning there may or may not be white-ish or gray-ish fluid oozing out of the tonsils.
The palatal petechiae is a result of damage done to the infected epithelial cells on the palate, and the hepatomegaly and splenomegaly are a result of the liver and spleen being lymph tissues through which infected B cells flow as cytotoxic T cells try to kill them, causing those organs to swell up.
The splenomegaly, though rare, is of particular importance because an enlarged spleen is more susceptible to rupture, and splenic rupture can result in excessive bleeding and even death.
Another rare symptom of mono is a rash with faint, non-itchy, pink macules or patches that show up on the trunk and arms.
A different type of rash that can be similar to this can occur if an individual with mono is misdiagnosed with a group A streptococcus infection, more commonly known as strep throat.
In this case, the person is given the antibiotics, ampicillin or amoxicillin, and, for some unknown reason, they develop an itchy maculopapular rash.
It is important to note this is not an allergic reaction because those individuals, after recovering from mono, can take ampicillin or amoxicillin for other infections and tolerate them just fine, not developing the itchy rash.
Diagnosis of infectious mononucleosis is initially suspected clinically based on signs and symptoms such as fever, sore throat, swollen cervical lymph nodes, and fatigue.
Then, a clinician would perform a peripheral blood smear, which would reveal the presence of atypical lymphocytes, most of which are enlarged cytotoxic (CD8+) T cells.
The diagnosis is then confirmed with a positive Monospot test, also called a heterophile antibody test. Heterophile antibodies are antibodies made by the infected B cells.
They are called “heterophile” or “other-loving” because they bind antigens from other animal species. In this case, they bind antigens on sheep or horse red blood cells, causing agglutination, or clumping, of the red blood cells and a positive test result.
In some cases, false-negatives of the Monospot test may occur, such as in early infections, in which heterophile antibodies have not yet been produced in high enough quantities to be detected, or in children under the age of 4, whose B cells may not produce heterophile antibodies at all.
In the case of an early infection, an individual can simply undergo the Monospot test again at a later time, after the infection progresses a bit, but for young children, testing for EBV-specific antibodies is the next step.
The EBV-specific antibody whose presence indicates an acute infection and can help confirm a mono diagnosis is the IgM viral capsid antigen antibody, or IgM VCA antibody.
This is an antibody against EBV’s capsid or protein coat. Other EBV-specific antibodies that can be tested for are IgG antibodies to EBV nuclear antigen, or EBNA, which only show up long after symptoms have resolved, and are markers of a latent infection.
Usually symptoms resolve on their own within a few weeks. So treatment includes rest, acetaminophen and non-steroidal anti-inflammatory drugs to help reduce fever and alleviate throat pain, avoiding contact with others, as EBV infection is highly contagious, and avoiding contact sports for at least 3 to 4 weeks, to prevent splenic rupture.
Rarely, EBV infections can extend beyond just causing mono. Most of the time, latently-infected B cells are killed by cytotoxic T cells.
Sometimes, though, cytotoxic T cells are unable to kill off infected B cells effectively, and infected B cells survive longer.
When this happens, there is an increased likelihood that the surviving infected B cells, in their latency, will express viral genes that produce protein products that result in increased B cell proliferation.
This can lead to B cell cancers, or B cell lymphomas, including both Hodgkin lymphoma and non-Hodgkin lymphoma, especially Burkitt Lymphoma and primary central nervous system lymphoma.
Similarly, EBV-infected epithelial cells can sometimes enter the latent phase, express viral genes that result in increased cell proliferation, and lead to nasopharyngeal carcinoma, a cancer of the upper part of the throat.
In immunocompromised individuals, such as those with HIV, the inability of cytotoxic T cells to kill EBV-infected B cells is especially pronounced, and B cell cancer development is more likely.
Additionally, individuals with HIV who are exposed to EBV may develop oral hairy leukoplakia, which appears as a white plaque on the lateral side of the tongue that cannot be scraped off.##Summary All right, as a quick recap: most of the time, Epstein-Barr virus causes asymptomatic latent infections of B cells, but sometimes, it can cause acute symptoms of fever, sore throat, enlarged lymph nodes, and fatigue, collectively called infectious mononucleosis or mono, which normally resolves on its own.
It can also lead to cancers including nasopharyngeal carcinoma, Hodgkin lymphoma, and non-Hodgkin lymphoma, especially Burkitt lymphoma and primary