Active replication of Middle East respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis.
Middle East respiratory syndrome coronavirus (MERS-CoV) infection caused severe pneumonia and multiorgan dysfunction and had a higher crude fatality rate (around 50% vs. 10%) than SARS coronavirus (SARS-CoV) infection. To understand the pathogenesis, we studied viral replication, cytokine/chemokine response, and antigen presentation in MERS-CoV-infected human monocyte-derived macrophages (MDMs) versus SARS-CoV-infected MDMs. Only MERS-CoV can replicate in MDMs. Both viruses were unable to significantly stimulate the expression of antiviral cytokines (interferon α [IFN-α] and IFN-β) but induced comparable levels of tumor necrosis factor α and interleukin 6. Notably, MERS-CoV induced significantly higher expression levels of interleukin 12, IFN-γ, and chemokines (IP-10/CXCL-10, MCP-1/CCL-2, MIP-1α/CCL-3, RANTES/CCL-5, and interleukin 8) than SARS-CoV. The expression of major histocompatibility complex class I and costimulatory molecules were significantly higher in MERS-CoV-infected MDMs than in SARS-CoV-infected cells. MERS-CoV replication was validated by immunostaining of infected MDMs and ex vivo lung tissue. We conclusively showed that MERS-CoV can establish a productive infection in human macrophages. The aberrant induction of inflammatory cytokines/chemokines could be important in the disease pathogenesis.
State Key Laboratory of Emerging Infectious Diseases.
Jie
J
Zhou
Hin
H
Chu
Cun
C
Li
Bosco Ho-Yin
BH
Wong
Zhong-Shan
ZS
Cheng
Vincent Kwok-Man
VK
Poon
Tianhao
T
Sun
Candy Choi-Yi
CC
Lau
Kenneth Kak-Yuen
KK
Wong
Jimmy Yu-Wai
JY
Chan
Jasper Fuk-Woo
JF
Chan
Kelvin Kai-Wang
KK
To
Kwok-Hung
KH
Chan
Bo-Jian
BJ
Zheng
Kwok-Yung
KY
Yuen
D000818:Animals; D017951:Antigen Presentation; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D017934:Coronavirus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D018352:Coronavirus Infections / Q000276:immunology / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D011024:Pneumonia, Viral / Q000276:immunology / Q000821:virology*; D014709:Vero Cells; D014779:Virus Replication / Q000502:physiology*
D016207:Cytokines
MERS-CoV; SARS-CoV; cytokine and chemokine response; pathogenesis; viral replication