CD8 as a receptor for primary human immuno-deficiency virus 1 (HIV-1).
Int Conf AIDS 2000 Jul 9-14; 13:32 (abstract no.. LbPeA7002)
Saha K, Dave R, Gupta A, Zhang J, Zerhouni B Children's Research Institute/OSU, Columbus, OH 43205. Fax: 614-722-3273, E-mail: sahak@pediatrics.ohio-state.edu.
HIV-1 uses CD4 as a receptor to infect CD4+ T cells and monocytes/macrophages. Although previous studies have shown that occasional CD8+ cells may become infected with HIV-1, it was assumed that HIV-1 entered these cells using CD4 receptors either expressed transiently in CD8+ cells or in double-positive T cells. We have isolated multiple CD8+ clones from an AIDS patient that are productively infected with HIV-1. Here we characterize two HIV-1 isolates produced by CD8+ clones and demonstrate that these viruses used CD8 as a receptor to infect CD8+ cells. Even though these viruses maintained ability to infect CD4+ cells, virus replication in CD8+ cells matched or exceeded to that of CD4+ cells indicating that CD8+ cells are targets for these viruses. In addition, these viruses were able to infect bona fide CD8+ T-cell line independent of CD4 further indicating that CD8+ cells are targets for these viruses. Several lines of evidence show that these viruses were able to infect CD8+ cells by using CD8 as a receptor. First, resistant cells (HeLa, COS) became susceptible to these viruses after expression of human CD8 molecules. Second, monoclonal anfi-CD8 antibodies were able to prevent viral entry into CD8+ cells. Third, expression of CD8 was down-modulated after infection with these viruses and anti-CD8 antibodies inhibited virus replication in purified CD8+ cells. Interestingly, antibodies against CXCR4 or CCR5 had no effect on infection with these viruses indicating that these co-receptors may play no role in infection. Finally, the envelope sequences of these viruses showed novel changes in the variable (V) loops and cluster them in a unique phylogenetic position. These results provide evidence for the first time that HIV-1 has the ability to change tropism in vivo and can target CD8+ cells using CD8 as a receptor. Direct infection of CD8+ cells by HIV-1 may play a critical role in the eventual failure of these cells to protect against AIDS.
Keywords: AEGIS, Antigens, CD8, HIV-1, CD8-Positive T-Lymphocytes, Antigens, CD4, CD4-Positive T-Lymphocytes, Virus Replication, Acquired Immunodeficiency Syndrome, T-Lymphocytes, Cell Line, Macrophages, Case-Control Studies, Greece, Human, immunology, virology, AIDS
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LbPeA7002
