TY - JOUR
T1 - Upregulation of IFN-stimulated genes persists beyond the transitory broad immunologic changes of acute HIV-1 infection
AU - for the Partners in Prevention HSV/HIV Transmission Study
AU - the Partners PrEP Study Teams
AU - Mackelprang, Romel D.
AU - Filali-Mouhim, Abdelali
AU - Richardson, Brian
AU - Lefebvre, Francois
AU - Katabira, Elly
AU - Ronald, Allan
AU - Gray, Glenda
AU - Cohen, Kristen W.
AU - Klatt, Nichole R.
AU - Pecor, Tiffany
AU - Celum, Connie
AU - McElrath, M. Juliana
AU - Hughes, Sean M.
AU - Hladik, Florian
AU - Cameron, Mark J.
AU - Lingappa, Jairam R.
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/4/21
Y1 - 2023/4/21
N2 - Chronic immune activation during HIV-1 infection contributes to morbidity and mortality in people living with HIV. To elucidate the underlying biological pathways, we evaluated whole blood gene expression trajectories from before, through acute, and into chronic HIV-1 infection. Interferon-stimulated genes, including MX1, IFI27 and ISG15, were upregulated during acute infection, remained elevated into chronic infection, and were strongly correlated with plasma HIV-1 RNA as well as TNF-α and CXCL10 cytokine levels. In contrast, genes involved in cellular immune responses, such as CD8A, were upregulated during acute infection before reaching a peak and returning to near pre-infection levels in chronic infection. Our results indicate that chronic immune activation during HIV-1 infection is characterized by persistent elevation of a narrow set of interferon-stimulated genes and innate cytokines. These findings raise the prospect of devising a targeted intervention to restore healthy immune homeostasis in people living with HIV-1.
AB - Chronic immune activation during HIV-1 infection contributes to morbidity and mortality in people living with HIV. To elucidate the underlying biological pathways, we evaluated whole blood gene expression trajectories from before, through acute, and into chronic HIV-1 infection. Interferon-stimulated genes, including MX1, IFI27 and ISG15, were upregulated during acute infection, remained elevated into chronic infection, and were strongly correlated with plasma HIV-1 RNA as well as TNF-α and CXCL10 cytokine levels. In contrast, genes involved in cellular immune responses, such as CD8A, were upregulated during acute infection before reaching a peak and returning to near pre-infection levels in chronic infection. Our results indicate that chronic immune activation during HIV-1 infection is characterized by persistent elevation of a narrow set of interferon-stimulated genes and innate cytokines. These findings raise the prospect of devising a targeted intervention to restore healthy immune homeostasis in people living with HIV-1.
KW - Immunology
KW - Molecular physiology
KW - Virology
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UR - http://www.scopus.com/inward/citedby.url?scp=85151257546&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.106454
DO - 10.1016/j.isci.2023.106454
M3 - Article
C2 - 37020953
AN - SCOPUS:85151257546
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 4
M1 - 106454
ER -
