SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys

Michael Humbert, Robert A. Rasmussen, Ruijiang Song, Helena Ong, Prachi Sharma, Agnès L. Chenine, Victor G. Kramer, Nagadenahalli B. Siddappa, Weidong Xu, James G. Else, Francis J. Novembre, Elizabeth Strobert, Shawn P. O'Neil, Ruth M. Ruprecht

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Abstract

Background: Infection of nonhuman primates with simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency virus (SHIV) strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide. Results: We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123-270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis. Conclusion: These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described (Song et al., 2006), display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.

Original languageEnglish (US)
Article number94
JournalRetrovirology
Volume5
DOIs
StatePublished - Oct 17 2008

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Simian Immunodeficiency Virus
Macaca mulatta
HIV-1
Acquired Immunodeficiency Syndrome
HIV
Viruses
Primates
AIDS Vaccines
Haplorhini
Cercopithecine Herpesvirus 1
Opportunistic Infections
Pandemics
Encephalitis
HIV Infections
Antiviral Agents
Disease Progression
Immunity
Clone Cells
Pediatrics
Infection

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Humbert, M., Rasmussen, R. A., Song, R., Ong, H., Sharma, P., Chenine, A. L., ... Ruprecht, R. M. (2008). SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys. Retrovirology, 5, [94]. https://doi.org/10.1186/1742-4690-5-94

SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys. / Humbert, Michael; Rasmussen, Robert A.; Song, Ruijiang; Ong, Helena; Sharma, Prachi; Chenine, Agnès L.; Kramer, Victor G.; Siddappa, Nagadenahalli B.; Xu, Weidong; Else, James G.; Novembre, Francis J.; Strobert, Elizabeth; O'Neil, Shawn P.; Ruprecht, Ruth M.

In: Retrovirology, Vol. 5, 94, 17.10.2008.

Research output: Contribution to journalArticle

Humbert, M, Rasmussen, RA, Song, R, Ong, H, Sharma, P, Chenine, AL, Kramer, VG, Siddappa, NB, Xu, W, Else, JG, Novembre, FJ, Strobert, E, O'Neil, SP & Ruprecht, RM 2008, 'SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys', Retrovirology, vol. 5, 94. https://doi.org/10.1186/1742-4690-5-94
Humbert, Michael ; Rasmussen, Robert A. ; Song, Ruijiang ; Ong, Helena ; Sharma, Prachi ; Chenine, Agnès L. ; Kramer, Victor G. ; Siddappa, Nagadenahalli B. ; Xu, Weidong ; Else, James G. ; Novembre, Francis J. ; Strobert, Elizabeth ; O'Neil, Shawn P. ; Ruprecht, Ruth M. / SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys. In: Retrovirology. 2008 ; Vol. 5.
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abstract = "Background: Infection of nonhuman primates with simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency virus (SHIV) strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide. Results: We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123-270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis. Conclusion: These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described (Song et al., 2006), display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.",
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AU - Humbert, Michael

AU - Rasmussen, Robert A.

AU - Song, Ruijiang

AU - Ong, Helena

AU - Sharma, Prachi

AU - Chenine, Agnès L.

AU - Kramer, Victor G.

AU - Siddappa, Nagadenahalli B.

AU - Xu, Weidong

AU - Else, James G.

AU - Novembre, Francis J.

AU - Strobert, Elizabeth

AU - O'Neil, Shawn P.

AU - Ruprecht, Ruth M.

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N2 - Background: Infection of nonhuman primates with simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency virus (SHIV) strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide. Results: We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123-270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis. Conclusion: These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described (Song et al., 2006), display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.

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