Variation in simian immunodeficiency virus env is confined to V1 and V4 during progression to simian AIDS

Overbaugh, Julie; Rudensey, Lyle M.; Papenhausen, Mark; Benveniste, R E; Morton, William R.

doi:10.1128/jvi.65.12.7025-7031.1991

Cited by 169 publications

(112 citation statements)

References 32 publications

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“…Nine to twenty clones from each sample were sequenced by dideoxy sequencing using Sequenase (U.S. Biochemical, Cleveland, OH). From previous experiments in our laboratory we have determined the rate of nucleotide mis-incorporation by Tuq polymerase to be similar to that reported by other laboratories [9].…”

Section: Rt-pcrsupporting

confidence: 81%

“…Viral genotypes were identified by sequence analysis of the first hypervariable region (Vl) of the SIV envelope gene after direct PCR amplification from PBMC or lymphoid tissue. Sequence analysis of this region was employed because it is one of the most hypervariable regions of the viral genome [5,9] and thus provides a good indicator of the number of genotypes present. Twelve genotypes differing by more than 4% in nucleotide sequence were identified in the SIVDeltaB670 inoculum by analysis of cloned PCR products of viral cDNA [l].…”

Section: Transplacental Transmissionmentioning

confidence: 99%

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Genotypic analysis of infant macaques infected transplacentally and orally

Amedee

Lacour

Martin

et al. 1996

J of Medical Primatology

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The SIV‐infected macaque provides an excellent model to study factors involved in maternal‐fetal transmission of HIV. In our prenatal transmission studies, female macaques were inoculated intravenously during midgestation with either SIV/DeltaB670 or a combination of SIV/DeltaB670 and the macrophage‐tropic molecular clone SIV/17E‐Fr. The females harbored a genetically diverse virus population at parturition, whereas a single genotype from the maternal quasispecies was identified in the infants. One of two variants was transplacentally transmitted to the infants, SIV/17E‐Fr or B670‐Cl 12, a genotype contained within the SIV/DeltaB670 inoculum. Both of these variants have been identified in the central nervous system of macaques that have developed encephalitis and they replicate in vitro on primary rhesus macrophages. These results suggest a critical role for macrophages in fetal infection in utero. In our perinatal transmission studies we have evaluated the viral genotypes found in two newborn macaques infected orally with SIV/DeltaB670 and in one infant infected via amniotic inoculation in late gestation. More than one viral genotype was identified in each infant, moreover, each infant harbored different genotypes. These results suggest different mechanisms are responsible for viral infection via these routes.

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Section: Rt-pcrsupporting

confidence: 81%

Section: Transplacental Transmissionmentioning

confidence: 99%

Genotypic analysis of infant macaques infected transplacentally and orally

Amedee

Lacour

Martin

et al. 1996

J of Medical Primatology

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“…(1,2) were grown in complete RPMI 1640 media (GIBCO, Grand Island, N.Y.) containing 10% heat-inactivated fetal calf serum (HyClone Laboratories, Logan, Utah) and supplemented with glutamine (Rl0 medium). Both EllS and the molecular clone derived from it have been shown to be infectious and pathogenic in multiple macaques species (24,39). Peripheral blood was obtained from normal Macaca nemestrina by venipuncture.…”

mentioning

confidence: 99%

T-cell activation influences initial DNA synthesis of simian immunodeficiency virus in resting T lymphocytes from macaques

Polacino

Liang

Firpo

et al. 1993

J Virol

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The relationship between T-cell activation and early events in the replication cycle of simian immunodeficiency virus (SIV) was analyzed in resting T lymphocytes from macaques. We used the polymerase chain reaction to detect an early product of reverse transcription (R/U5) and almost complete viral DNA (long terminal repeat/gag). We found that SIV can enter resting T lymphocytes and initiate replication but that the reverse transcription process is not efficient and proceeds slowly in resting cells. Cross-linking the CD3/T-cell receptor complex with monoclonal antibodies, unlike cross-linking either the CD28 or CD2 accessory receptor and like phorbol myristate acetate, induced a rapid increase in viral R/U5 DNA detected within 3 to 6 h postinfection. Anti-CD3 or phorbol myristate acetate induced replication of full-length viral DNA within 6 to 9 h postinfection, but full-length SIV DNA was not detectable at earlier time points. We then compared various inhibitors of T-cell activation for their effects on viral initiation and complete replication. Cyclosporin A, an inhibitor of a distal step in T-cell activation, blocked anti-CD3-induced T-cell proliferation and completion of SIV DNA replication but had no effect on induced increases in SIV R/U5 DNA. By contrast, initial SIV DNA synthesis was partially blocked by inhibitors of very early steps in T-cell activation, including herbimycin A, an inhibitor of protein tyrosine kinases, and by two different inhibitors of protein kinase C, H7 and staurosporine. Since resting T cells do not efficiently complete SIV DNA synthesis and cyclosporin A can block the formation of complete viral DNA induced in activated T cells, a cellular factor(s) present in activated T cells appears to be required for the formation of full-length SIV DNA.

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“…In the macaque model, inoculation of moleculary cloned SIV allowed estimation of nucleotide variation over time (Burns & Desrosiers 1991, Johnson et al 1991, Overbaugh et al 1991. The variation was especially large in the envelope gene, where nucleotide substitution frequencies were as high as 10"'/site year.…”

Section: Introductionmentioning

confidence: 99%

Antigenic Variation of Primate Lentiviruses in Humans and Experimentally Infected Macaques

Fenyõ¹

1994

Immunological Reviews

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Neutralizing antibodies in primate lentivirus infections closely parallel the pathogenic process. Fast progression to disease is concomitant with lack of neutralizing antibodies to autologous virus. Slow or no progression to disease is linked with production of neutralizing antibodies to autologous virus. Moreover, there is evidence from the monkey model that the extent to which neutralizing antibodies cross-react may also be linked with the pathogenic process. Accordingly, slow progression to disease is associated with the capacity to neutralize several isolates and, conversely, fast progressors neutralize single autologous isolates, if any at all. In humans, transmission of HIV-1 from mother to child occurs more frequently in absence of autologous and/or heterologous neutralizing antibodies to primary isolates. Thus there is evidence that virus neutralization-perhaps in concert with the biological properties of the virus-is an important factor in primate lentivirus pathogenesis and transmission. Open questions are i) the extent of heterologous neutralization in slow or nonprogressor HIV-1- and HIV-2-infected individuals, ii) role of neutralizing antibodies in sexual transmission, and iii) what governs the specificity, broad or narrow, of the neutralizing antibody response in different hosts. If we can answer these questions we may be able to design preventive measures against HIV infection and/or disease. Studies on the interaction of virus and immune system in the infected host may therefore not only teach us about the pathogenetic process, but also help in developing an HIV vaccine.

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Variation in simian immunodeficiency virus env is confined to V1 and V4 during progression to simian AIDS

Cited by 169 publications

References 32 publications

Genotypic analysis of infant macaques infected transplacentally and orally

Genotypic analysis of infant macaques infected transplacentally and orally

T-cell activation influences initial DNA synthesis of simian immunodeficiency virus in resting T lymphocytes from macaques

Antigenic Variation of Primate Lentiviruses in Humans and Experimentally Infected Macaques

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