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103 Identification of HIV-2 Strains That Do Not Use CCR5 or CXCR4 to Enter in Peripheral Blood Mononuclear Cells
J. M. Azevedo-Pereira*1, Q. Santos-Costa1, K. Mansinho2, and J. Moniz-Pereira1
1Centro de Patogénese Molecular, Faculty of Pharmacy, Univ. of Lisbon, Portugal and 2Serviço de Doenças Infecciosas, Hosp. Egas Moniz, Portugal
Background: Like HIV-1, HIV-2 uses CD4 and chemokine receptors to enter cells. In this study we used coreceptor-targeted inhibitors to demonstrate that some HIV-2 strains do not use CCR5 or CXCR4 to enter in peripheral blood mononuclear cells (PBMC).
Materials and Methods: Chemokine receptors inhibitors used were: MAb 12G5, SDF-1alpha, RANTES, and MAb 2D7. Viruses were inoculated in CD8-depleted PBMC in the presence or absence of inhibitors. Viral production in PBMC and in GHOST and U87 cell lines were monitored by p24Ag production in culture supernatants.
Results: From a panel of 11 HIV-2 primary strains we identified 2 that were unable to productively infect any GHOST or U87 CD4-positive cells expressing several chemokine receptors. These 2 strains can infect PBMC even in the presence of the coreceptor inhibitors 12G5, 2D7, RANTES, and SDF-1alpha. Our data indicate that these isolates obtained from asymptomatic individuals do not use CCR5 or CXCR4 to enter in PBMC.
Conclusions: We conclude that HIV-2 could establish a human infection, without using CCR5 or CXCR4. In these cases an alternative coreceptor, present in PBMC but absent in GHOST or U87 chemokine receptor-expressing cells, should be used. This finding could have important implications in HIV-2 pathogenesis and transmission.
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