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HIV/AIDS Pathogenesis: Limited HIV evolution in persistently targeted CD8 epitopes in chronic infection

AIDSWEEKLY Plus; Monday, October 3, 2005
Staff Medical Writers


NewsRx -- There is limited viral evolution within persistently targeted CD8 T cell epitopes in chronic HIV-1 infection.

According to a study from the United States, "Studies in acute human immunodeficiency virus type 1 (HIV-1) infection indicate viral evolution under CD8 T-cell immune selection pressure, but the effects of ongoing immune pressure on epitope evolution during chronic infection are not well described.

"In this study, we performed a detailed longitudinal analysis of viral sequence variation within persistently targeted cytotoxic T-lymphocyte (CTL) epitopes in two HIV-1-infected persons during 6 years of persistent viremia."

"Responses were quantitated using freshly isolated peripheral blood lymphocytes in direct lytic assays as well as by gamma interferon (IFN-gamma) Elispot assays on cryopreserved cells. Seven targeted epitopes were identified in each person.

"In the majority of cases," wrote T. Koibuchi and colleagues at Harvard Medical School, "the dominant epitope sequence did not change over time, even in the presence of responses of sufficient magnitude that they were detectable using fresh peripheral blood mononuclear cells in direct lytic assays."

"Only 4 of the 14 autologous epitopes tested represented potential CTL escape variants; however, in most cases strong responses to these epitopes persisted for the 6 years of study," investigators reported.

"Although persistent IFN-gamma responses were detected to all epitopes," continued Koibuchi, "direct lytic assays demonstrated declining responses to some epitopes despite the persistence of the targeted sequence in vivo."

Scientists concluded, "These data indicate limited viral evolution within persistently targeted CD8 T-cell epitopes during the chronic phase of infection and suggest that these regions of the virus are either refractory to sequence change or that persistently activated CD8 T-cell responses in chronic infection exert little functional selection pressure."

Koibuchi and colleagues published the results of their research in the Journal of Virology (Limited sequence evolution within persistently targeted CD8 epitopes in chronic human immunodeficiency virus type 1 infection. J Virol, 2005;79(13):8171-81).

For additional information, contact T. Koibuchi, and Division of AIDS, Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

The publisher of the Journal of Virology can be contacted at: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

Keywords: Boston, Massachusetts, United States, HIV/AIDS, Sequence Evolution, CD8 Epitopes, Chronic Infection.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Koibuchi T, Allen TM, Lichterfeld M, et al. Limited sequence evolution within persistently targeted CD8 epitopes in chronic human immunodeficiency virus type 1 infection., J Virol. 2005 Jul;79(13):8171-81.

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