Nicotinamide mononucleotide impacts HIV-1 infection by modulating immune activation in T lymphocytes and humanized mice
Yufei Mo, Ming Yue, Lok Yan Yim, Runhong Zhou, Chunhao Yu, Qiaoli Peng, Ying Zhou, Tsz‐Yat Luk, Grace Lui, Huarong Huang, Chun Yu Hubert Lim, Hui Wang, Li Liu, Hongzhe Sun, Jun Wang, You‐Qiang Song, Zhiwei Chen
Abstract
Background HIV-1-associated immune activation drives CD4 + T cell depletion and the development of acquired immunodeficiency syndrome. We aimed to determine the role of nicotinamide mononucleotide (NMN), the direct precursor of nicotinamide adenine dinucleotide (NAD) co-enzyme, in CD4 + T cell modulation during HIV-1 infection. Methods We examined HIV-1 integrated DNA or transcribed RNA, intracellular p24 protein, and T cell activation markers in CD4 + T cells including in vitro HIV-1-infected cells, reactivated patient-derived cells, and in HIV-1-infected humanized mice, under NMN treatment. RNA-seq and CyTOF analyses were used for investigating the effect of NMN on CD4 + T cells. Findings We found that NMN increased the intracellular NAD amount, resulting in suppressed HIV-1 p24 production and proliferation in infected CD4 + T cells, especially in activated CD25 + CD4 + T cells. NMN also inhibited CD25 expression on reactivated resting CD4 + T cells derived from cART-treated people living with HIV-1 (PLWH). In HIV-1-infected humanized mice, the frequency of CD4 + T cells was reconstituted significantly by combined cART and NMN treatment as compared with cART or NMN alone, which correlated with suppressed hyperactivation of CD4 + T cells. Interpretation Our results highlight the suppressive role of NMN in CD4 + T cell activation during HIV-1 infection. It warrants future clinical investigation of NMN as a potential treatment in combination with cART in PLWH. Funding This work was supported by the Hong Kong Research Grants Council Theme-Based Research Scheme (T11-706/18-N), University Research Committee of The University of Hong Kong, the Collaborative Research with GeneHarbor (Hong Kong) Biotechnologies Limited and National Key R&D Program of China (Grant2021YFC2301900).