Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo

Svetlana Glushakova, Jean Charles Grivel, Kalachar Suryanarayana, Pascal Meylan, Jeffrey D. Lifson, Ronald Desrosiers, Leonid Margolis

Research output: Contribution to journalArticle

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Abstract

The nef gene is important for the pathogenicity associated with simian immunodeficiency virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (HIV-1) infection in humans. The mechanisms by which nef contributes to pathogenesis in vivo remain unclear. We investigated the contribution of nef to HIV-1 replication in human lymphoid tissue ex vivo by studying infection with parental HIV-1 strain NL4-3 and with a nef mutant (ΔnefNL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than ΔnefNL4-3 did. Increased virus production with NL4-3 infection was associated with increased numbers of productively infected cells and greater loss of CD4 + T cells over time. While the numbers of productively infected T cells were increased in the presence of nef, the levels of vital expression and production per infected T cell were similar whether the nef gene was present or not. Exogenous interleukin-2 (IL-2) increased HIV-1 production in NL-3-infected tissue in a dose-dependent manner. In contrast, ΔnefNL4-3 production was enhanced only marginally by IL-2. Thus, Nef can facilitate HIV-1 replication in human lymphoid tissue ex vivo by increasing the numbers of productively infected cells and by increasing the responsiveness to IL-2 stimulation.

Original languageEnglish
Pages (from-to)3968-3974
Number of pages7
JournalJournal of Virology
Volume73
Issue number5
Publication statusPublished - 1999
Externally publishedYes

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Lymphoid Tissue
Virus Replication
Interleukin-2
HIV-1
HIV
nef Genes
Virus Diseases
T-Lymphocytes
Simian Immunodeficiency Virus
Infection
Macaca mulatta
Virulence
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Glushakova, S., Grivel, J. C., Suryanarayana, K., Meylan, P., Lifson, J. D., Desrosiers, R., & Margolis, L. (1999). Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo. Journal of Virology, 73(5), 3968-3974.

Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo. / Glushakova, Svetlana; Grivel, Jean Charles; Suryanarayana, Kalachar; Meylan, Pascal; Lifson, Jeffrey D.; Desrosiers, Ronald; Margolis, Leonid.

In: Journal of Virology, Vol. 73, No. 5, 1999, p. 3968-3974.

Research output: Contribution to journalArticle

Glushakova, S, Grivel, JC, Suryanarayana, K, Meylan, P, Lifson, JD, Desrosiers, R & Margolis, L 1999, 'Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo', Journal of Virology, vol. 73, no. 5, pp. 3968-3974.
Glushakova, Svetlana ; Grivel, Jean Charles ; Suryanarayana, Kalachar ; Meylan, Pascal ; Lifson, Jeffrey D. ; Desrosiers, Ronald ; Margolis, Leonid. / Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo. In: Journal of Virology. 1999 ; Vol. 73, No. 5. pp. 3968-3974.
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