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Diverse effects of interferon alpha on the establishment and reversal of HIV latency

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Renée M Van der Sluis
  • Jennifer M Zerbato, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.
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  • Jake W Rhodes, Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Road, Sydney, New South Wales 2145, Australia.
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  • Rachel D Pascoe, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.
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  • Ajantha Solomon, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.
  • ,
  • Nitasha A Kumar, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.
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  • Ashanti I Dantanarayana, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.
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  • Surekha Tennakoon, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.
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  • Jérémy Dufloo, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.
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  • James McMahon, Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia.
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  • Judy J Chang, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.
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  • Vanessa A Evans, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.
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  • Paul J Hertzog, Dept Molecular & Translational Sciences, Monash University, Clayton, VIC, Australia.
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  • Martin R Jakobsen
  • Andrew N Harman, Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Road, Sydney, New South Wales 2145, Australia.
  • ,
  • Sharon R Lewin, Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia.
  • ,
  • Paul U Cameron, Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia.

HIV latency is the major barrier to a cure for people living with HIV (PLWH) on antiretroviral therapy (ART) because the virus persists in long-lived non-proliferating and proliferating latently infected CD4+ T cells. Latently infected CD4+ T cells do not express viral proteins and are therefore not visible to immune mediated clearance. Therefore, identifying interventions that can reverse latency and also enhance immune mediated clearance is of high interest. Interferons (IFNs) have multiple immune enhancing effects and can inhibit HIV replication in activated CD4+ T cells. However, the effects of IFNs on the establishment and reversal of HIV latency is not understood. Using an in vitro model of latency, we demonstrated that plasmacytoid dendritic cells (pDC) inhibit the establishment of HIV latency through secretion of type I IFNα, IFNβ and IFNω but not IFNε or type III IFNλ1 and IFNλ3. However, once latency was established, IFNα but no other IFNs were able to efficiently reverse latency in both an in vitro model of latency and CD4+ T cells collected from PLWH on suppressive ART. Binding of IFNα to its receptor expressed on primary CD4+ T cells did not induce activation of the canonical or non-canonical NFκB pathway but did induce phosphorylation of STAT1, 3 and 5 proteins. STAT5 has been previously demonstrated to bind to the HIV long terminal repeat and activate HIV transcription. We demonstrate diverse effects of interferons on HIV latency with type I IFNα; inhibiting the establishment of latency but also reversing HIV latency once latency is established.

OriginalsprogEngelsk
Artikelnummere1008151
TidsskriftPLOS Pathogens
Vol/bind16
Nummer2
Antal sider27
ISSN1553-7366
DOI
StatusUdgivet - 2020

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