title: Predominance of defective proviral sequences in an HIV + long-term non-progressor.
abstract: We examined the accessory genes and envelope V3 region of provirus obtained over a 5 year period from an HIV+ long-term non-progressor with very low viral load and no in vitro recoverable virus during that same time span. LTR sequences supported normal Tat-mediated promoter activity. Multiple clones of nef sequences were highly conserved with < 10% containing frame shift or stop codon mutations. Functional analysis of the predominant nef sequence indicated wild type downregulation of surface CD4 and good function in a complementation infectivity assay. By contrast, inactivating mutations were found in 64% of amplicons containing vif, vpr, vpu, tat1, and rev1, and in 41% of amplicons containing env V3. Identical inactive sequences were obtained at an interval of 2 years, suggesting persistence of quiescent defective provirus in a long-lived clonal cell population. Furthermore, genetic distance versus time analysis revealed an absence of progressive evolution or arborization of quasispecies over time. This contrasts with data generated from other asymptomatic HIV+ individuals. The non-progressive pattern of env sequence diversity and low R2 for genetic divergence over time suggests that the defective provirus circulating in the periphery of this patient represents a randomly sampled 'fossil record' of earlier replication competent HIV-1 genomes.
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Schwartz
authors.forename: R
authors.initials: R
authors.lastname: Viscidi
authors.forename: O
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: H
authors.initials: H
authors.lastname: Song
authors.forename: S C
authors.initials: SC
authors.lastname: Ray
authors.forename: N
authors.initials: N
authors.lastname: Michael
mesh_terms: D003673:Defective Viruses / Q000235:genetics*; D005260:Female; D015693:Gene Products, nef / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics; D011533:Proviruses / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics*; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D014759:Viral Envelope Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus