Short-lived infected cells support virus replication in sooty mangabeys naturally infected with simian immunodeficiency virus: Implications for AIDS pathogenesis

Shari N. Gordon, Richard M. Dunham, Jessica C. Engram, Jacob Estes, Zichun Wang, Nichole R. Klatt, Mirko Paiardini, Ivona V. Pandrea, Cristian Apetrei, Donald L. Sodora, Ha Youn Lee, Ashley T. Haase, Michael D. Miller, Amitinder Kaur, Silvija I. Staprans, Alan S. Perelson, Mark B. Feinberg, Guido Silvestri

Research output: Contribution to journalArticle

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Abstract

Sooty mangabeys (SMs) naturally infected with simian immunodeficiency virus (SIV) do not develop AIDS despite high levels of virus replication. At present, the mechanisms underlying this disease resistance are poorly understood. Here we tested the hypothesis that SIV-infected SMs avoid immunodeficiency as a result of virus replication occurring in infected cells that live significantly longer than human immunodeficiency virus (HIV)-infected human cells. To this end, we treated six SIV-infected SMs with potent antiretroviral therapy (ART) and longitudinally measured the decline in plasma viremia. We applied the same mathematical models used in HIV-infected individuals and observed that SMs naturally infected with SIV also present a two-phase decay of viremia following ART, with the bulk (92 to 99%) of virus replication sustained by short-lived cells (average life span, 1.06 days), and only 1 to 8% occurring in longer-lived cells. In addition, we observed that ART had a limited impact on CD4 + T cells and the prevailing level of T-cell activation and proliferation in SIV-infected SMs. Collectively, these results suggest that in SIV-infected SMs, similar to HIV type 1-infected humans, short-lived activated CD4+ T cells, rather than macrophages, are the main source of virus production. These findings indicate that a short in vivo life span of infected cells is a common feature of both pathogenic and nonpathogenic primate lentivirus infections and support a model for AIDS pathogenesis whereby the direct killing of infected cells by HIV is not the main determinant of disease progression.

Original languageEnglish (US)
Pages (from-to)3725-3735
Number of pages11
JournalJournal of Virology
Volume82
Issue number7
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

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Cercocebus atys
Cercocebus
Simian immunodeficiency virus
Simian Immunodeficiency Virus
Virus Replication
virus replication
Acquired Immunodeficiency Syndrome
pathogenesis
Human immunodeficiency virus
T-lymphocytes
Viremia
viremia
HIV
cells
T-Lymphocytes
therapeutics
Lentivirus Infections
Primate Lentiviruses
Lentivirus
Disease Resistance

ASJC Scopus subject areas

  • Immunology

Cite this

Short-lived infected cells support virus replication in sooty mangabeys naturally infected with simian immunodeficiency virus : Implications for AIDS pathogenesis. / Gordon, Shari N.; Dunham, Richard M.; Engram, Jessica C.; Estes, Jacob; Wang, Zichun; Klatt, Nichole R.; Paiardini, Mirko; Pandrea, Ivona V.; Apetrei, Cristian; Sodora, Donald L.; Lee, Ha Youn; Haase, Ashley T.; Miller, Michael D.; Kaur, Amitinder; Staprans, Silvija I.; Perelson, Alan S.; Feinberg, Mark B.; Silvestri, Guido.

In: Journal of Virology, Vol. 82, No. 7, 01.04.2008, p. 3725-3735.

Research output: Contribution to journalArticle

Gordon, SN, Dunham, RM, Engram, JC, Estes, J, Wang, Z, Klatt, NR, Paiardini, M, Pandrea, IV, Apetrei, C, Sodora, DL, Lee, HY, Haase, AT, Miller, MD, Kaur, A, Staprans, SI, Perelson, AS, Feinberg, MB & Silvestri, G 2008, 'Short-lived infected cells support virus replication in sooty mangabeys naturally infected with simian immunodeficiency virus: Implications for AIDS pathogenesis', Journal of Virology, vol. 82, no. 7, pp. 3725-3735. https://doi.org/10.1128/JVI.02408-07
Gordon, Shari N. ; Dunham, Richard M. ; Engram, Jessica C. ; Estes, Jacob ; Wang, Zichun ; Klatt, Nichole R. ; Paiardini, Mirko ; Pandrea, Ivona V. ; Apetrei, Cristian ; Sodora, Donald L. ; Lee, Ha Youn ; Haase, Ashley T. ; Miller, Michael D. ; Kaur, Amitinder ; Staprans, Silvija I. ; Perelson, Alan S. ; Feinberg, Mark B. ; Silvestri, Guido. / Short-lived infected cells support virus replication in sooty mangabeys naturally infected with simian immunodeficiency virus : Implications for AIDS pathogenesis. In: Journal of Virology. 2008 ; Vol. 82, No. 7. pp. 3725-3735.
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abstract = "Sooty mangabeys (SMs) naturally infected with simian immunodeficiency virus (SIV) do not develop AIDS despite high levels of virus replication. At present, the mechanisms underlying this disease resistance are poorly understood. Here we tested the hypothesis that SIV-infected SMs avoid immunodeficiency as a result of virus replication occurring in infected cells that live significantly longer than human immunodeficiency virus (HIV)-infected human cells. To this end, we treated six SIV-infected SMs with potent antiretroviral therapy (ART) and longitudinally measured the decline in plasma viremia. We applied the same mathematical models used in HIV-infected individuals and observed that SMs naturally infected with SIV also present a two-phase decay of viremia following ART, with the bulk (92 to 99{\%}) of virus replication sustained by short-lived cells (average life span, 1.06 days), and only 1 to 8{\%} occurring in longer-lived cells. In addition, we observed that ART had a limited impact on CD4 + T cells and the prevailing level of T-cell activation and proliferation in SIV-infected SMs. Collectively, these results suggest that in SIV-infected SMs, similar to HIV type 1-infected humans, short-lived activated CD4+ T cells, rather than macrophages, are the main source of virus production. These findings indicate that a short in vivo life span of infected cells is a common feature of both pathogenic and nonpathogenic primate lentivirus infections and support a model for AIDS pathogenesis whereby the direct killing of infected cells by HIV is not the main determinant of disease progression.",
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AU - Gordon, Shari N.

AU - Dunham, Richard M.

AU - Engram, Jessica C.

AU - Estes, Jacob

AU - Wang, Zichun

AU - Klatt, Nichole R.

AU - Paiardini, Mirko

AU - Pandrea, Ivona V.

AU - Apetrei, Cristian

AU - Sodora, Donald L.

AU - Lee, Ha Youn

AU - Haase, Ashley T.

AU - Miller, Michael D.

AU - Kaur, Amitinder

AU - Staprans, Silvija I.

AU - Perelson, Alan S.

AU - Feinberg, Mark B.

AU - Silvestri, Guido

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