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J. Virol., 12 1995, 7507-7518, Vol 69, No. 12
Copyright © 1995, American Society for Microbiology

Naturally occurring accessory gene mutations lead to persistent human immunodeficiency virus type 1 infection of CD4-positive T cells

M Kishi, YH Zheng, MK Bahmani, K Tokunaga, H Takahashi, M Kakinuma, PK Lai, M Nonoyama, RB Luftig and K Ikuta
Section of Serology, Hokkaido University, Sapporo, Japan.

Proviral DNA from cells surviving severe but transient cytopathic effects, mediated by infection with recombinant human immunodeficiency virus type 1 (HIV-1) carrying a single gene mutation at vif, vpr, or vpu, was characterized by use of HIV-1-specific primer pairs in a two- step PCR. Deletion mutations were detected in a region that spanned the vif and vpr open reading frames. Cloning and sequencing of the amplified DNA from this region revealed frequent large deletions in a limited number of nucleotide positions. Analyses of the deletions suggested that (i) genetic recombination, (ii) template-primer slippage, and (iii) misalignment of the growing point during reverse transcription of the HIV-1 genome might be the mechanisms that generated the mutations. Apart from the large deletions, smaller deletions that gave frameshift mutations in vif and/or vpr prevailed. In addition, cells infected with a triple mutant defective in vif, vpr, and vpu did not show any cytopathic effect. Thus, mutations generating multiple accessory gene defects during HIV-1 replication correlate with viral persistence and loss of cytopathogenicity.

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