title: Retroviral recombination in vivo: viral replication patterns and genetic structure of simian immunodeficiency virus (SIV) populations in rhesus macaques after simultaneous or sequential intravaginal inoculation with SIVmac239Deltavpx/Deltavpr and SIVmac239Deltanef.
abstract: To characterize the occurrence, frequency, and kinetics of retroviral recombination in vivo, we intravaginally inoculated rhesus macaques, either simultaneously or sequentially, with attenuated simian immunodeficiency virus (SIV) strains having complementary deletions in their accessory genes and various degrees of replication impairment. In monkeys inoculated simultaneously with SIVmac239Deltavpx/Deltavpr and SIVmac239Deltanef, recombinant wild-type (wt) virus and wild-type levels of plasma viral RNA (vRNA) were detected in blood by 2 weeks postinoculation. In monkeys inoculated first with SIVmac239Deltavpx/Deltavpr and then with SIVmac239Deltanef, recombination occurred but was associated with lower plasma vRNA levels than plasma vRNA levels seen for monkeys inoculated intravaginally with wt SIVmac239. In one monkey, recombination occurred 6 weeks after the challenge with SIVmac239Deltanef when plasma SIVmac239Deltavpx/Deltavpr RNA levels were undetectable. In monkeys inoculated first with the more highly replicating strain, SIVmac239Deltanef, and then with SIVmac239Deltavpx/Deltavpr, wild-type recombinant virus was not detected in blood or tissues. Instead, a virus that had repaired the deletion in the nef gene by a compensatory mutation was found in one animal. Overall, recombinant SIV was eventually found in four of six animals intravaginally inoculated with the two SIVmac239 deletion mutants. These findings show that recombination can occur readily in vivo after mucosal SIV exposure and thus contributes to the generation of viral genetic diversity and enhancement of viral fitness.
authors.affiliation: Division of Infectious Diseases, The Feinberg School of Medicine at Northwestern University, Chicago, Illinois, USA.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Marc
authors.initials: M
authors.lastname: Busch
authors.forename: Kristina
authors.initials: K
authors.lastname: Abel
authors.forename: Linda
authors.initials: L
authors.lastname: Fritts
authors.forename: Patty
authors.initials: P
authors.lastname: Bustamante
authors.forename: Jenny
authors.initials: J
authors.lastname: Stanton
authors.forename: Ding
authors.initials: D
authors.lastname: Lu
authors.forename: Samuel
authors.initials: S
authors.lastname: Wu
authors.forename: Jenny
authors.initials: J
authors.lastname: Glowczwskie
authors.forename: Tracy
authors.initials: T
authors.lastname: Rourke
authors.forename: Derek
authors.initials: D
authors.lastname: Bogdan
authors.forename: Mike
authors.initials: M
authors.lastname: Piatak
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Desrosiers
authors.forename: Steven
authors.initials: S
authors.lastname: Wolinsky
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D005260:Female; D015686:Gene Products, env / Q000008:administration & dosage / Q000276:immunology*; D016336:Gene Products, vpr / Q000235:genetics*; D005814:Genes, Viral; D015754:Genes, nef; D014644:Genetic Variation; D005838:Genotype; D007267:Injections; D007371:Interferon-gamma / Q000276:immunology; D008253:Macaca mulatta; D012367:RNA, Viral / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000008:administration & dosage / Q000276:immunology*; D017384:Sequence Deletion; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014621:Vagina; D014760:Viral Fusion Proteins / Q000008:administration & dosage / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics*
chemical_list: D015686:Gene Products, env; D016336:Gene Products, vpr; D012367:RNA, Viral; D015682:Retroviridae Proteins, Oncogenic; D014760:Viral Fusion Proteins; C059580:transmembrane protein, Simian immunodeficiency virus; D007371:Interferon-gamma