title: Recombination-mediated changes in coreceptor usage confer an augmented pathogenic phenotype in a nonhuman primate model of HIV-1-induced AIDS.
abstract: Evolution of the env gene in transmitted R5-tropic human immunodeficiency virus type 1 (HIV-1) strains is the most widely accepted mechanism driving coreceptor switching. In some infected individuals, however, a shift in coreceptor utilization can occur as a result of the reemergence of a cotransmitted, but rapidly controlled, X4 virus. The latter possibility was studied by dually infecting rhesus macaques with X4 and R5 chimeric simian simian/human immunodeficiency viruses (SHIVs) and monitoring the replication status of each virus using specific primer pairs. In one of the infected monkeys, both SHIVs were potently suppressed by week 12 postinoculation, but a burst of viremia at week 51 was accompanied by an unrelenting loss of total CD4+ T cells and the development of clinical disease. PCR analyses of plasma viral RNA indicated an env gene segment containing the V3 region from the inoculated X4 SHIV had been transferred into the genetic background of the input R5 SHIV by intergenomic recombination, creating an X4 virus with novel replicative, serological, and pathogenic properties. These results indicate that the effects of retrovirus recombination in vivo can be functionally profound and may even occur when one of the recombination participants is undetectable in the circulation as cell-free virus.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Shingai
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Lee
authors.forename: Reza
authors.initials: R
authors.lastname: Sadjadpour
authors.forename: Olivia K
authors.initials: OK
authors.lastname: Donau
authors.forename: Ronald
authors.initials: R
authors.lastname: Willey
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: Ranjini
authors.initials: R
authors.lastname: Iyengar
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Martin
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D008253:Macaca mulatta; D015728:Receptors, HIV / Q000378:metabolism*; D011995:Recombination, Genetic; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity*; D014766:Viremia; D053586:Virus Internalization
chemical_list: D015728:Receptors, HIV