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Article: Enhanced infectivity of an R5-tropic simian/human immunodeficiency virus carrying human immunodeficiency virus type 1 subtype C envelope after serial passages in pig-tailed macaques (Macaca nemestrina)

TitleEnhanced infectivity of an R5-tropic simian/human immunodeficiency virus carrying human immunodeficiency virus type 1 subtype C envelope after serial passages in pig-tailed macaques (Macaca nemestrina)
Authors
Issue Date2000
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2000, v. 74 n. 14, p. 6501-6510 How to Cite?
AbstractThe increasing prevalence of human immunodeficiency virus type 1 (HIV-1) subtype C infection worldwide calls for efforts to develop a relevant animal model for evaluating strategies against the transmission of the virus. A chimeric simian/human immunodeficiency virus (SHIV), SHIV(CHN)19, was generated with a primary, non-syncytium-inducing HIV-1 subtype C envelope from a Chinese strain in the background of SHIV33. Unlike R5-tropic SHIV162, SHIV(CHN)19 was not found to replicate in rhesus CD4+ T lymphocytes. SHIV(CHN)19 does, however, replicate in CD4+ T lymphocytes of pig-tailed macaques (Macaca nemestrina). The observed replication competence of SHIV(CHN)19 requires the full tat/rev genes and partial gp41 region derived from SHIV33. To evaluate in vivo infectivity, SHIV(CHN)19 was intravenously inoculated, at first, into two pig-tailed and two rhesus macaques. Although all four animals became infected, the virus replicated preferentially in pig-tailed macaques with an earlier plasma viral peak and a faster seroconversion. To determine whether in vivo adaptation would enhance the infectivity of SHIV(CHN)19, passages were carried out serially in three groups of two pig-tailed macaques each, via intravenous blood-bone marrow transfusion. The passages greatly enhanced the infectivity of the virus as shown by the increasingly elevated viral loads during acute infection in animals with each passage. Moreover, the doubling time of plasma virus during acute infection became much shorter in passage 4 (P4) animals (0.2 day) in comparison to P1 animals (1 to 2 days). P2 to P4 animals all became seropositive around 2 to 3 weeks postinoculation and had a decline in CD4/CD8 T-cell ratio during the early phase of infection. In P4 animals, a profound depletion of CD4 T cells in the lamina propria of the jejunum was observed. Persistent plasma viremia has been found in most of the infected animals with sustained viral loads ranging from 103 to 105 per ml up to 6 months postinfection. Serial passages did not change the viral phenotype as confirmed by the persistence of the R5 tropism of SHIV(CHN)19 isolated from P4 animals. In addition, the infectivity of SHIV(CHN)19 in rhesus peripheral blood mononuclear cells was also increased after in vivo passages. Our data indicate that SHIV(CHN)19 has adapted well to grow in macaque cells. This established R5-tropic SHIV(CHN)19/macaque model would be very useful for HIV-1 subtype C vaccine and pathogenesis studies.
Persistent Identifierhttp://hdl.handle.net/10722/157310
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChen, Zen_US
dc.contributor.authorHuang, Yen_US
dc.contributor.authorZhao, Xen_US
dc.contributor.authorSkulsky, Een_US
dc.contributor.authorLin, Den_US
dc.contributor.authorIp, Jen_US
dc.contributor.authorGettie, Aen_US
dc.contributor.authorHo, DDen_US
dc.date.accessioned2012-08-08T08:48:50Z-
dc.date.available2012-08-08T08:48:50Z-
dc.date.issued2000en_US
dc.identifier.citationJournal Of Virology, 2000, v. 74 n. 14, p. 6501-6510en_US
dc.identifier.issn0022-538Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/157310-
dc.description.abstractThe increasing prevalence of human immunodeficiency virus type 1 (HIV-1) subtype C infection worldwide calls for efforts to develop a relevant animal model for evaluating strategies against the transmission of the virus. A chimeric simian/human immunodeficiency virus (SHIV), SHIV(CHN)19, was generated with a primary, non-syncytium-inducing HIV-1 subtype C envelope from a Chinese strain in the background of SHIV33. Unlike R5-tropic SHIV162, SHIV(CHN)19 was not found to replicate in rhesus CD4+ T lymphocytes. SHIV(CHN)19 does, however, replicate in CD4+ T lymphocytes of pig-tailed macaques (Macaca nemestrina). The observed replication competence of SHIV(CHN)19 requires the full tat/rev genes and partial gp41 region derived from SHIV33. To evaluate in vivo infectivity, SHIV(CHN)19 was intravenously inoculated, at first, into two pig-tailed and two rhesus macaques. Although all four animals became infected, the virus replicated preferentially in pig-tailed macaques with an earlier plasma viral peak and a faster seroconversion. To determine whether in vivo adaptation would enhance the infectivity of SHIV(CHN)19, passages were carried out serially in three groups of two pig-tailed macaques each, via intravenous blood-bone marrow transfusion. The passages greatly enhanced the infectivity of the virus as shown by the increasingly elevated viral loads during acute infection in animals with each passage. Moreover, the doubling time of plasma virus during acute infection became much shorter in passage 4 (P4) animals (0.2 day) in comparison to P1 animals (1 to 2 days). P2 to P4 animals all became seropositive around 2 to 3 weeks postinoculation and had a decline in CD4/CD8 T-cell ratio during the early phase of infection. In P4 animals, a profound depletion of CD4 T cells in the lamina propria of the jejunum was observed. Persistent plasma viremia has been found in most of the infected animals with sustained viral loads ranging from 103 to 105 per ml up to 6 months postinfection. Serial passages did not change the viral phenotype as confirmed by the persistence of the R5 tropism of SHIV(CHN)19 isolated from P4 animals. In addition, the infectivity of SHIV(CHN)19 in rhesus peripheral blood mononuclear cells was also increased after in vivo passages. Our data indicate that SHIV(CHN)19 has adapted well to grow in macaque cells. This established R5-tropic SHIV(CHN)19/macaque model would be very useful for HIV-1 subtype C vaccine and pathogenesis studies.en_US
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_US
dc.relation.ispartofJournal of Virologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCd4 Lymphocyte Counten_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshGene Products, Env - Genetics - Metabolismen_US
dc.subject.meshHiv-1 - Genetics - Metabolism - Pathogenicityen_US
dc.subject.meshInjections, Intravenousen_US
dc.subject.meshMacaca Nemestrinaen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshSimian Immunodeficiency Virus - Genetics - Metabolism - Pathogenicityen_US
dc.subject.meshViral Loaden_US
dc.subject.meshViremia - Blooden_US
dc.subject.meshVirus Replicationen_US
dc.titleEnhanced infectivity of an R5-tropic simian/human immunodeficiency virus carrying human immunodeficiency virus type 1 subtype C envelope after serial passages in pig-tailed macaques (Macaca nemestrina)en_US
dc.typeArticleen_US
dc.identifier.emailChen, Z:zchenai@hkucc.hku.hken_US
dc.identifier.authorityChen, Z=rp00243en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1128/JVI.74.14.6501-6510.2000en_US
dc.identifier.pmid10864663-
dc.identifier.scopuseid_2-s2.0-0033934367en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033934367&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume74en_US
dc.identifier.issue14en_US
dc.identifier.spage6501en_US
dc.identifier.epage6510en_US
dc.identifier.isiWOS:000087817900032-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChen, Z=35271180800en_US
dc.identifier.scopusauthoridHuang, Y=7501575029en_US
dc.identifier.scopusauthoridZhao, X=8781942500en_US
dc.identifier.scopusauthoridSkulsky, E=6506978838en_US
dc.identifier.scopusauthoridLin, D=36785688000en_US
dc.identifier.scopusauthoridIp, J=16947098600en_US
dc.identifier.scopusauthoridGettie, A=7003730114en_US
dc.identifier.scopusauthoridHo, DD=7402971998en_US

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