2011
DOI: 10.1128/jvi.05010-11
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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 replicati… Show more

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Cited by 9 publications
(5 citation statements)
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“…Importantly, recombination can also pair advantageous mutations, which can facilitate the acquisition of multidrug resistance leading to treatment failure (48)(49)(50)(51)(52)(53)(54). Recombination may also be an important mechanism by which the virus eventually escapes immune control (55)(56)(57)(58). However, recombination also has the potential to inhibit adaptation and evolution depending on epistasis and genetic drift (51).…”
Section: Discussionmentioning
confidence: 99%
“…Importantly, recombination can also pair advantageous mutations, which can facilitate the acquisition of multidrug resistance leading to treatment failure (48)(49)(50)(51)(52)(53)(54). Recombination may also be an important mechanism by which the virus eventually escapes immune control (55)(56)(57)(58). However, recombination also has the potential to inhibit adaptation and evolution depending on epistasis and genetic drift (51).…”
Section: Discussionmentioning
confidence: 99%
“…Recombination increases overall genetic complexity of viral populations more than just the accumulation of site mutations alone, thereby raising the likelihood for recombinants to find favorable genetic configurations and facilitating faster adaptation 4 . Recombination is believed to contribute to viral diversity and fitness 5 7 , drug resistance 8 , 9 , immunological escape 10 , 11 , and disease progression 7 , 12 .…”
Section: Introductionmentioning
confidence: 99%
“…The infectious titers of SHIVAD8 -CE8J , SHIV AD8-CK15 , and SHIV AD8-CL98 were 1.83 ϫ 10 4 50% tissue culture infective doses (TCID 50 )/ml, 4.09 ϫ 10 4 TCID 50 /ml, and 3.49 ϫ 10 5 TCID 50 /ml, respectively, as determined in Rh PBMC. The replication kinetics of these viral stocks were evaluated by spinoculating (1,200 ϫ g for 1 h) ConA-stimulated PBMC with these virus stocks, following normalization for 32 P-RT activity (33). Virus replication was assessed by 32 P-RT assay of the culture supernatant.…”
Section: Methodsmentioning
confidence: 99%
“…For intracellular cytokine assays, immune stimulation using SIVmac239 Gag peptides (New England Peptide, Gardner, MA), 15 amino acids in length, was performed on frozen or freshly prepared lymphocytes as described previously (33).…”
Section: Methodsmentioning
confidence: 99%