3rd Conference on Retroviruses and Opportunistic Infections


Washington, DC - January 28-February 1, 1996

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VIF NEGATIVE HIV-1 PERSISTENTLY REPLICATES IN PRIMARY MACROPHAGES PRODUCING ATTENUATED VIRUS.

Conf Retroviruses Opportunistic Infect 1996 Jan 28-Feb 1; 3rd:61 (abstract no. 47)

Chowdhury IH, Potash MJ, Chao W, Sova P, Volsky DJ
St. Luke's/Roosevelt Hospital, Columbia University, NY.

The vif gene of human immunodeficiency virus type 1 (HIV-1) is required for efficient infection of primary T lymphocytes. In this study we investigated in detail the role of vif in productive infection of primary monocyte derived macrophages (MDM). Viruses carrying mutations in vif were constructed on the background of the monocytotropic recombinant NLHXADA-GP. Using MDM from multiple donors we found that vif mutants are approximately 10% as infectious as wildtype virus when assayed for incomplete, complete, and circularized viral DNA molecules by quantitative polymerase chain reaction amplification or for viral core antigen p24 production by Elisa. To determine the structure and infectivity of vif mutant HIV-1 produced by MDM, progeny viruses were examined by biosynthetic labeling and radioimmunoprecipitation or by passage to uninfected macrophages or to transformed T cells. Although considerably reduced in p24 content, progeny virions were able to establish infection in macrophages as determined by synthesis and maintenance of full length viral DNA, by the production of particulate associated viral RNA, and by rescue of infectious virus in T cells. Infectivity of vif negative HIV-1 produced by MDM was reduced approximately 2,100 fold compared to wildtype virus titrated in parallel by viral DNA burden. We conclude that mutations in vif result in the establishment of persistent, attenuated HIV-1 infection in macrophages which may be relevant to the maintenance of a chronic, semi-latent infection in vivo.

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