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Vif negative HIV-1 persistently replicates in primary macrophages producing attenuated virus.




 

3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:61. Unique

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.

Enzyme-Linked Immunosorbent Assay Gene Products, vif/GENETICS/*METABOLISM HIV Core Protein p24/BIOSYNTHESIS HIV-1/METABOLISM/*PHYSIOLOGY/PATHOGENICITY Human Macrophages/*VIROLOGY Mutation Polymerase Chain Reaction Radioimmunoprecipitation Assay Virus Replication ABSTRACT



 




Information in this article was accurate in November 30, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.