Upregulation of IFN-stimulated genes persists beyond the transitory broad immunologic changes of acute HIV-1 infection
Romel D. Mackelprang,
Abdelali Filali-Mouhim,
Brian Richardson,
Francois Lefebvre,
Elly Katabira,
Allan Ronald,
Glenda Gray,
Kristen W. Cohen,
Nichole R. Klatt,
Tiffany Pecor,
Connie Celum,
M. Juliana McElrath,
Sean M. Hughes,
Florian Hladik,
Mark J. Cameron,
Jairam R. Lingappa
Affiliations
Romel D. Mackelprang
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Corresponding author
Abdelali Filali-Mouhim
University of Montreal Hospital Research Center, Laval, QC, Canada
Brian Richardson
Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
Francois Lefebvre
Canadian Centre for Computational Genomics, McGill University, Montreal, QC, Canada
Elly Katabira
Infectious Disease Institute, Makerere University, Kampala, Uganda
Allan Ronald
Canada Departments of Medical Microbiology and Internal Medicine, University of Manitoba, Winnipeg, MB, USA
Glenda Gray
Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa
Kristen W. Cohen
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Nichole R. Klatt
Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
Tiffany Pecor
Washington National Primate Research Center, Seattle, WA, USA
Connie Celum
Department of Global Health, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
M. Juliana McElrath
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Sean M. Hughes
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA
Florian Hladik
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
Mark J. Cameron
Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
Jairam R. Lingappa
Department of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA
Summary: 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.
