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MERS induces apoptosis in human T cells, offering new therapeutic target
Middle East respiratory syndrome coronavirus, or MERS-CoV, has the unique ability to both infect T cells and induce apoptosis, which may explain the high pathogenicity of the virus, according to Chinese researchers.
“MERS-CoV infection in T cells induced massive apoptosis involving activation of both the extrinsic and intrinsic apoptosis pathways, which might be important in the pathogenesis of MERS,” Hin Chu, PhD, from the State Key Laboratory of Emerging Infectious Diseases at the University of Hong Kong, and colleagues wrote.
To test whether T cells are potential targets of MERS-CoV, Chu and colleagues introduced MERS-CoV into peripheral blood mononuclear cells. Using flow cytometry, the researchers measured the amount of infected T cells, B cells, natural killer cells and monocytes. MERS-CoV infected a large number of T cells (65.6% + 5.4%); however, the virus was found less often in monocytes (13.5% + 6.6%) and natural killer cells (18.5% + 4.8%). B cells were rarely infected (5.4% + 2.4%), according to the researchers.
The level of MERS-CoV infection was related to the level of surface dipeptidyl peptidase-4 (DPP4), a MERS-CoV receptor.
MERS-CoV easily infected T cells, specifically CD4+ and CD8+ cells; however, the same results were not seen with SARS-CoV, the researchers said. In addition, MERS-CoV “significantly down-regulated surface DPP4 in infected CD4+ T cells by 80% and CD8+ T cells by 70%.”
Chu and colleagues found that MERS-CoV induced T cell apoptosis, and that the virus activated the extrinsic and intrinsic apoptosis pathways.
“Their seminal findings could give a novel perspective for the immunopathogenesis of MERS-CoV and could partly explain the lymphopenia observed in MERS-CoV-infected patients,” Tianlei Ying, PhD, from Shanghai Medical College, and colleagues wrote in an accompanying editorial.
Furthermore, the researchers found that T cells in human lymphoid organs, such as the spleen and tonsils, were highly susceptible to MERS-CoV infection.
“Collectively, our ex vivo and in vivo findings suggest that MERS-CoV can invade not only T cells in the peripheral blood, but also the large repertoire of T cells in lymphoid organs, which may result in a more severe immunopathology,” Chu and colleagues wrote. “We demonstrated that the infection is associated with apoptosis induction, the findings of which may provide a new target for effective therapeutic interventions.” – by Colleen Owens
Disclosure: The researchers report no relevant financial disclosures. Ying and colleagues report no relevant financial disclosures.