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GEN News Highlights : Apr 2, 2010

CMV’s Ability to Re-Infect Is Linked to Evasion of Killer T-Cell Recruitment

Findings may hinder anti-CMV vaccine development but could be leveraged for applications in the viral vector field, as reported in Science.

Scientists may have unraveled the mechanism by which cytomegalovirus (CMV) can re-infect people who have previously been persistently infected and developed strong, long-lasting immune responses against the virus. Studies in CMV-infected macaques by a team at Oregon Health & Science University Vaccine and Gene Therapy Institute (OHSU VGTI) now suggest that CMV re-infection occurs because the virus can evade recognition by the body’s natural CD8+ T cells, or killer T cells.

Louis Picker, M.D., associate director of the OHSU VGTI and VGTI vaccine program director, suggests that while their findings highlight that significant barriers will need to be overcome if a preventive CMV vaccine is to be developed, the same phenomenon may mean CMV represents a potentially useful viral vaccine vector. Their research is published in Science in a paper titled “Evasion of CD8+ T Cells Is Critical for Superinfection by Cytomegalovirus.”

CMV is one of the few virus types that can efficiently re-infect individuals who are already persistently infected by this virus. How the virus can circumvent the immune system has to date remained unclear, the Oregon team states. The researchers’ studies in macaques now suggest that the phenomenon is linked to the virus’ ability to make genes that disrupt the ability of killer T cells to recognize infected cells.

Killer T cells are normally recruited to the site of a viral infection by MHC-1 molecules expressed on infected cells. Dr. Picker’s work suggests, however, that CMV circumvents this part of the immune system by making genes that disrupt the MHC-1 molecules’ ability to communicate an ongoing infection to the T cells. “In essence, CMV is able to cut off an infected cell’s call for elimination,” explains co-author Klaus Frueh, Ph.D. “This allows CMV to overcome this critical immune barrier during re-infection.”

While this finding does not spell good news for anti-CMV vaccine development, it could be harnessed for the development of repeat-use vaccine vectors, the authors conclude.