From the Guidelines
Epstein-Barr virus (EBV) is the virus most notably associated with latent infection and expression of some, but not all, viral genes in B lymphocytes. During latent infection, EBV persists in B cells while expressing a limited set of viral genes, including Epstein-Barr nuclear antigens (EBNAs), latent membrane proteins (LMPs), and viral non-coding RNAs 1. This restricted gene expression allows the virus to avoid detection by the immune system while maintaining its presence in the host. EBV establishes different latency programs (types I, II, and III) in B cells, each characterized by distinct patterns of viral gene expression 1. The ability to establish latency in B lymphocytes is central to EBV's lifecycle and its association with various diseases, including infectious mononucleosis, Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disorders.
Some key points to consider:
- EBV typically spreads through saliva and initially infects epithelial cells before establishing latency in B cells, where it can remain for the lifetime of the host 1.
- The diagnosis of EBV-PTLD must be based on symptoms and/or signs consistent with PTLD together with detection of EBV by an appropriate method applied to a specimen from the involved tissue 1.
- EBV detection requires in situ hybridization for the EBER transcripts or detection of viral antigens 1.
- The use of rituximab should be restricted to patients at highest risk of EBV-PTLD and, following its use, accompanied by close monitoring for hypogammaglobulinemia with consideration of Ig replacement and other strategies to limit infectious-related mortality 1.
- Antiviral drugs have shown some in vitro activity against replicating EBV, but antiviral treatment of latent EBV has been unsuccessful since latently infected B cells do not express the EBV thymidine kinase enzyme transcript or protein 1.
Overall, the association of EBV with latent infection and expression of some, but not all, viral genes in B lymphocytes is a critical aspect of its lifecycle and disease association. Understanding the mechanisms of EBV latency and its implications for disease diagnosis and treatment is essential for managing EBV-related disorders effectively.
From the Research
Latent Infection in B Lymphocytes
- The virus associated with latent infection and expression of some (but not all) viral genes in B lymphocytes is Epstein-Barr virus (EBV) 2, 3, 4, 5, 6.
Expression of Viral Genes
- Upon infection of B cells with EBV, the virus induces cellular proliferation and establishes a latent infection, expressing a subset of latent viral genes 2.
- The early events in primary human B cells infected with EBV involve the initial but transient expression of additional viral genes that do not belong to the 'classical' latent subset 2.
- Some of these viral genes have been known to initiate the lytic, productive phase of EBV, but virus synthesis does not take place early after infection 2.
Role of EBNA2
- EBNA2 is essential for activating naive human B lymphocytes, inducing their growth, driving them into rapid cell divisions, and preventing cell death in a subset of infected cells 3.
- EBNA2 governs the infected cells initially and implements a strictly controlled temporal program independent of other viral latent genes 3.
Latency Types
- Latent virus infection of B lymphocytes can be classified into different types, including Type I, Type IIa, Type IIb, and Type III, each with distinct expression patterns of viral genes 4.
- Type IIa cells express LMP-1 but not EBNA-2, while Type IIb cells express EBNA-2 but not LMP-1 4.
- Type III cells express all latent viral genes, including EBNA-2 and LMP-1 4.