Simian immunodeficiency virus Nef gene regulates the production of 2-LTR circles in vivo.
The replication dynamics of simian immunodeficiency virus (SIVmac32H-C8), attenuated through discrete genetic disruption of the nef gene, were compared with the wild-type parental clone (SIVmac32H-J5) using quantitative molecular methods. The primary viraemia of both infections were similar during the first week, but peaked on Day 10 at higher levels for wild-type virus. Viral RNA levels differed most markedly at Day 14. The frequency and levels of viral DNA species, detectable as gag provirus or circular 2-LTR episomes, differed depending on the virus and the lymphoid compartment sampled. 2-LTR circles persisted for prolonged periods in the peripheral blood but were never detected in any SIVmac32H C8-infected tissue, even if positive by gag PCR. Paradoxically, the converse was observed following wild-type infection. 2-LTR circles disappeared from the peripheral blood by Day 42 postinfection but persisted in lymphoid tissues. These findings are discussed in terms of nef and the role and stability of 2-LTR circle forms in vivo.
Clarke
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S
Division of Retrovirology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, EN6 3QG, Herts, UK.
Almond
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N
Berry
N
N
D000818:Animals; D004279:DNA, Viral / Q000097:blood; D015967:Gene Expression Regulation, Viral; D015683:Gene Products, gag / Q000097:blood; D015754:Genes, nef; D008221:Lymphoid Tissue / Q000821:virology; D008252:Macaca fascicularis; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D020079:Terminal Repeat Sequences / Q000235:genetics / Q000502:physiology*; D014766:Viremia / Q000821:virology; D014779:Virus Replication
D004279:DNA, Viral; D015683:Gene Products, gag; D012367:RNA, Viral