In a study that will be appeared on the coming issue of Nature Microbiology, a research team led by Drs. Ke Zen and Chen-Yu Zhang from Nanjing University School of Life Sciences, China, reports that human cytomegalovirus (HCMV) reprograms human hematopoietic progenitor cells (HPCs) into a unique monocyte subset to achieve its latent infection. This work is a collaborative project with Professor Fenyong Liu at University of California at Berkeley, and Professor Jianguo Wu at Wuhan University School of Life Sciences.
HCMV is a widespread pathogen and can establish life-long latent infection in a large population. Although HCMV reactivation from the latency is normally asymptomatic in a healthy person, it can be fatal for immunocompromised individuals such as AIDS patients and organ transplant recipients. The precise cell type harboring latent HCMV in human body remains elusive. Although it is widely accepted that HCMV achieves natural latency in CD34+ HPCs, HCMV infection will lead to cell differentiation of primitive HPCs. In other words, it is unclear what cell type the HCMV-infected HPCs would become when HCMV establish latency.
In the present study, Zhu et al. reveal that via activating STAT3/iNOS/NO axis HCMV differentiates human HPCs into a longevous, immunosuppressive monocyte subset for viral latency. More interestingly, they further identified several surface proteins unique for the cells that host latent HCMV, and employing one of the marker protein, B7-H4, they successfully sorted out the population of latent HCMV-harbouring monocytes from the peripheral blood of donors latently infected with HCMV. This small population of immunosuppressive monocyte subset only occupied about 1% of total peripheral blood mononuclear cells. Identification of marker for HCMV latently infected cells certainly will be helpful to eliminate HCMV latency and consequent viral reactivation.
Another interesting point is that they found the immunosuppressive capacity of this unique monocyte subset that host HCMV latency. As evading the T cell immune response is critical for HCMV latency, the immunosuppressive function processed by the cells hosting HCMV latency may be a key for HCMV to maintain the latent infection.
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The researchers of this project include Dihan Zhu, Chaoyun Pan, Jingxue Sheng, Hongwei Liang, Zhen Bian, Yuan Liu, Phong Trang, Jianguo Wu, Fenyong Liu2, Chen-Yu Zhang, and Ke Zen, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Nanjing, Jiangsu 210093, China; School of Public Health, University of California, Berkeley, CA 94720, USA; Center for Inflammation, Infection Diseases and Immunology, Georgia State University, Atlanta, GA 30302, USA; State Key Laboratory of Virology, Wuhan University School of Life Sciences, Wuhan, Hubei 430072, China. This work was supported by grants from National Basic Research Program of China (973 Program) (2014CB542300), National Natural Science Foundation of China (81101330, 31271378, 81250044 and 31600659), Research Special Fund for Public Welfare Industry of Health (201302018) and NIH (RO1-AI050468, RO1-DE023935, and RO1-025462).
Journal
Nature Microbiology