Infection and depletion of CD4+ group-1 innate lymphoid cells by HIV-1 via type-I interferon pathway.

• Main Authors: Juanjuan Zhao, Liang Cheng, Hongbo Wang, Haisheng Yu, Bo Tu, Qiang Fu, Guangming Li, Qi Wang, Yanling Sun, Xin Zhang, Zhenwen Liu, Weiwei Chen, Liguo Zhang, Lishan Su, Zheng Zhang
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2018-01-01
• Series: PLoS Pathogens
• Online Access: http://europepmc.org/articles/PMC5773236?pdf=render

Innate lymphoid cells (ILCs) are severely depleted during chronic HIV-1 infection by unclear mechanisms. We report here that human ILC1s comprising of CD4+ and CD4- subpopulations were present in various human lymphoid organs but with different transcription programs and functions. Importantly, CD4+ ILC1s expressed HIV-1 co-receptors and were productively infected by HIV-1 in vitro and in vivo. Furthermore, chronic HIV-1 infection activated and depleted both CD4+ and CD4- ILC1s, and impaired their cytokine production activity. Highly active antiretroviral (HAART) therapy in HIV-1 patients efficiently rescued the ILC1 numbers and reduced their activation, but failed to restore their functionality. We also found that blocking type-I interferon (IFN-I) signaling during HIV-1 infection in vivo in humanized mice prevented HIV-1 induced depletion or apoptosis of ILC1 cells. Therefore, we have identified the CD4+ ILC1 cells as a new target population for HIV-1 infection, and revealed that IFN-I contributes to the depletion of ILC1s during HIV-1 infection.