Banner
    CD35: New B Cell Attachment Receptor For Epstein-Barr Virus Discovered
    By News Staff | February 21st 2013 05:14 PM | Print | E-mail | Track Comments

    The Epstein-Barr virus (EBV) is more accurately known as herpesvirus 4 (HHV-4), one of 8 viruses in the herpes family and one of the most common viruses in humans, affecting more than 90 percent of the population worldwide and over 95% of adults in America - so common it is almost hard to attribute it to anything. 

    The Epstein-Barr viruswas first discovered in the early 1960s. Infections in early childhood usually have no symptoms, but it remains for life and also people infected during adolescence or young adulthood may develop mononucleosis. It has been associated with Hodgkin's lymphoma, non-Hodgkin's lymphoma and nasopharyngeal carcinoma. 

    But efforts are on to create a vaccine to guard against EBV because of a possible relationship to malaria and autoimmune diseases and so research is continually being made into how the virus works.  Viruses must first attach to their host cells. For herpesviruses, receptors on the viral envelope become connected to complementary receptors on the cell membrane. In the case of EBV, the virus gains access to the immune system by attaching to primary B cells. Researchers have now discovered a second B-cell attachment receptor for EBV,  CD35. 

    "Our discovery that CD35 is an attachment receptor for EBV helps explain several previously unsolved observations," explains the study's senior author Joyce Fingeroth, MD, Associate Professor of Medicine at Harvard Medical School and member of the Division of Infectious Diseases group at Beth Israel Deaconess Medical Center. "EBV was the first human virus that was discovered to be a tumor virus. In fact, individuals who have had infectious mononucleosis have a four times increased risk of developing Hodgkin's disease."

    Nearly 30 years ago, Fingeroth was on the team that discovered that this attachment occurs via the CD21 protein, which until now was the only known B cell attachment receptor for EBV. The recent finding that B cells from a patient lacking CD21 can be infected and immortalized by EBV had indicated that an alternative attachment receptor must exist. 

    The identification of this second receptor, CD35, in work led by first author Javier Ogembo, PhD, of Beth Israel Deaconess Medical Center and the University of Massachusetts Medical School, not only underscores an important finding regarding primary infection but also underscores the importance of EBVgp350/220, (the virus protein that has been found to bind to both attachment receptors) for the development of a vaccine against EBV.

    "The EBV glycoprotein gp350/220 is the most abundant surface glycoprotein on the virus," notes Fingeroth, adding that these results further suggest the virus fusion apparatus is the same for both receptors. "An EBV vaccine might be able to prevent infection or, alternatively, greatly reduce a person's risk of developing infectious mononucleosis and EBV-associated cancers, without necessarily preventing the EBV infection itself."

    Whereas a human has now been identified to be lacking the CD21 receptor, no persons are known to lack CD35. 

    "CD35 is a latecomer in evolution and in its current form, exists only in humans," says Fingeroth. "We know that it is often targeted in autoimmune diseases and was recently identified as a malaria receptor. Our new discovery may, therefore, reveal new avenues for the exploration of unexplained links between EBV, autoimmune diseases, malaria and cancer."


    Citation: Javier G. Ogembo, Lakshmi Kannan, Ionita Ghiran, Anne Nicholson-Weller, Robert W. Finberg, George C. Tsokos, Joyce D. Fingeroth, 'Human Complement Receptor Type 1/CD35 Is an Epstein-Barr Virus Receptor', Cell Reports 3(2) pp. 371 - 385 DOI:10.1016/j.celrep.2013.01.023