Reduced Chronic Lymphocyte Activation following Interferon Alpha Blockade during the Acute Phase of Simian Immunodeficiency Virus Infection in Rhesus Macaques Article Swipe
Diane G. Carnathan
,
Benton Lawson
,
Joana Yu
,
Kalpana Patel
,
James M. Billingsley
,
Gregory K. Tharp
,
Olivia M. Delmas
,
Reem Dawoud
,
Peter Wilkinson
,
Charles A. Nicolette
,
Mark J. Cameron
,
Rafick‐Pierre Sékaly
,
Steven E. Bosinger
,
Guido Silvestri
,
Thomas H. Vanderford
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1128/jvi.01760-17
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1128/jvi.01760-17
Pathogenic human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection of humans and rhesus macaques (RMs) induces persistently high production of type I interferon (IFN-I), which is thought to contribute to disease progression. To elucidate the specific role of interferon alpha (IFN-α) in SIV pathogenesis, 12 RMs were treated prior to intravenous (i.v.) SIV mac239 infection with a high or a low dose of an antibody (AGS-009) that neutralizes most IFN-α subtypes and were compared with six mock-infused, SIV-infected controls. Plasma viremia was measured postinfection to assess the effect of IFN-α blockade on virus replication, and peripheral blood and lymphoid tissue samples were analyzed by immunophenotypic staining. Consistent with the known antiviral effect of IFN-I, high-dose AGS-009 treatment induced a modest increase in acute-phase viral loads versus controls. Four out of 6 RMs receiving a high dose of AGS-009 also experienced an early decline in CD4 + T cell counts that was associated with progression to AIDS. Interestingly, 50% of the animals treated with AGS-009 (6/12) developed AIDS within 1 year of infection compared with 17% (1/6) of untreated controls. Finally, blockade of IFN-α decreased the levels of activated CD4 + and CD8 + T cells, as well as B cells, as measured by PD-1 and/or Ki67 expression. The lower levels of activated lymphocytes in IFN-α-blockaded animals supports the hypothesis that IFN-α signaling contributes to lymphocyte activation during SIV infection and suggests that this signaling pathway is involved in controlling virus replication during acute infection. The potential anti-inflammatory effect of IFN-α blockade should be explored as a strategy to reduce immune activation in HIV-infected individuals. IMPORTANCE Interferon alpha (IFN-α) is a member of a family of molecules (type I interferons) that prevent or limit virus infections in mammals. However, IFN-α production may contribute to the chronic immune activation that is thought to be the primary cause of immune decline and AIDS in HIV-infected patients. The study presented here attempts to understand the contribution of IFN-α to the natural history and progression of SIV infection of rhesus macaques, the primary nonhuman primate model system for testing hypotheses about HIV infection in humans. Here, we show that blockade of IFN-α action promotes lower chronic immune activation but higher early viral loads, with a trend toward faster disease progression. This study has significant implications for new treatments designed to impact the type I interferon system.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1128/jvi.01760-17
- https://jvi.asm.org/content/jvi/92/9/e01760-17.full.pdf
- OA Status
- bronze
- Cited By
- 27
- References
- 32
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2790792396
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2790792396Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1128/jvi.01760-17Digital Object Identifier
- Title
-
Reduced Chronic Lymphocyte Activation following Interferon Alpha Blockade during the Acute Phase of Simian Immunodeficiency Virus Infection in Rhesus MacaquesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2018Year of publication
- Publication date
-
2018-02-19Full publication date if available
- Authors
-
Diane G. Carnathan, Benton Lawson, Joana Yu, Kalpana Patel, James M. Billingsley, Gregory K. Tharp, Olivia M. Delmas, Reem Dawoud, Peter Wilkinson, Charles A. Nicolette, Mark J. Cameron, Rafick‐Pierre Sékaly, Steven E. Bosinger, Guido Silvestri, Thomas H. VanderfordList of authors in order
- Landing page
-
https://doi.org/10.1128/jvi.01760-17Publisher landing page
- PDF URL
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https://jvi.asm.org/content/jvi/92/9/e01760-17.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
-
https://jvi.asm.org/content/jvi/92/9/e01760-17.full.pdfDirect OA link when available
- Concepts
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Simian immunodeficiency virus, Viremia, Biology, Virology, Immunology, Virus, CD8, Interferon, Viral replication, Pathogenesis, Lymphocyte, Alpha interferon, Immunodeficiency, Immune systemTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
27Total citation count in OpenAlex
- Citations by year (recent)
-
2024: 4, 2023: 3, 2022: 2, 2021: 6, 2020: 4Per-year citation counts (last 5 years)
- References (count)
-
32Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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