Introduction:
Epstein-Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is a member of the gammaherpesvirus family. EBV belongs to the gamma 1 or lymphocryptovirus genus and was identified as the first human tumor virus. EBV was first discovered in 1964 in Burkitt lymphoma (BL) and was later found to also be associated with other types of lymphoma including Hodgkin lymphoma (HL), non-HL in post-transplant patients and HIV-infected individuals, T cell lymphoma, and natural killer (NK)/T cell lymphoma. In addition to its association with different forms of human cancer, EBV is also linked with non-malignant disease including infectious mononucleosis (IM), oral hairy leukoplakia, systemic lupus erythematosus (SLE), and multiple sclerosis (MS). EBV infects over 95% of the world’s population and is a highly successful pathogen. Primary infection is often asymptomatic and occurs at a young age in developing countries and at a later age in more industrialized countries. EBV is intermittently shed in saliva in healthy individuals. In the USA, the seroprevalence of EBV antibody ranges from 50% in children to 89% in teenagers See Raab-Traub
EBV is of the and infects B cells. It’s limited host range (B cells) is due to the limited cellular expression of its receptor which is also the receptor for the C3d component of the . This receptor is expressed on and epithelial cells of the oropharynx and nasopharynx. The virus initially establishes a productive infection in the epithelial cells of the oropharynx and is then shed into the saliva (which can also transmit the virus) and accesses B lymphocytes in lymphatic tissue and blood.
The disease associated with EBV is called Infectious mononucleosis (IM) and is characterized by fever, malaise and lymphadenopathy. It is milder in children then adults.
Transcription & Replication:
EBV transmission primarily occurs through saliva. However, breast milk, bodily fluids, and transplantation of EBV-positive organs can also spread the virus from one host to another.
During latent infection, cells contain a small number of circular plasmids like EBV genomes that replicate only during cell division. Select immediate early genes are expressed including Epstein-Barr virus nuclear antigen-1 (EBNA-1) which binds OriP and unwinds DNA. Host then synthesize DNA.
Pathology:
EBV establishes life-long persistence in the human host by infecting B cells and residing in memory B cells in healthy people where it is asymptomatic and does not cause disease. However, both intrinsic factors (e.g., genetic mutations and deficiencies) and extrinsic factors (e.g., immunosuppression, HIV infection, salted or preserved fish diet) can result in the development of EBV-associated cancers.
Similar to other herpesviruses, EBV has two distinct phases of its life cycle—latency and lytic replication. During the latent phase, the virus is present in the nucleus as a circular episome tethered to the host genomic chromatin utilizing a viral protein named EBNA1. Under latent conditions, the virus expresses a small fraction of viral genes and non-coding RNAs and, depending on the cell type infected, distinct latent gene expression programs have been observed. During latency, the virus is dependent on normal cellular division processes, including the host DNA replication machinery, to passively replicate its viral genome and be transmitted to daughter cells.
Transmission:
EBV is acquired by close contact between persons through saliva. About 70% of the US population is infected with EBV by age 30. Depending on the cell type, different EBV glycoproteins participate in epithelial versus B cell infection. During B cell infection, EBV gp350/220 binds the complement receptor CD21 present on B cells, or it can also utilize another complement receptor, CD35.
Treatment:
There is no effective treatment for EBV. Latent viral DNA is unaffected by antiviral drugs because it is replicated by the host DNA polymerase complex. There is, however, life-long immunity. Thus there is no chance of getting a second infection as with HSV.