A novel Zika virus mouse model reveals strain specific differences in virus pathogenesis and host inflammatory immune responses.

Shashank Tripathi, Vinod R. M. T. Balasubramaniam, Adolfo GarcõÂa-Sastre, et al.

PLoS Pathog 2017 Mar. 9;13(3): e1006258

Speaker: Hua-Lin Wu (吳驊霖)                                    Time: 13:10~14:00, Dec. 27, 2017

Commentator: Dr. Shun-Hua Chen (陳舜華老師)       Place: Room 601

Abstract:

  Zika virus (ZIKV) is a member of Flavivirus, which is transmitted through mosquito of the Aedes genus. In recent years, it has been reported that ZIKV infection might be associated with fetal malformation and Guillain-Barré syndromes. ZIKV was first isolated in Uganda in 1947, but the first outbreak was occurred in Yap Island in 2007 ^[1]. Till 2015, ZIKV has spread across Africa, Asia, South and Central America, and got attention from then on. According to phylogenetic analysis, ZIKV can be classified into African and Asian lineages. However, it is still unknown whether there were differences in disease phenotype between two lineages of ZIKV. In authors’ previous studies, they have demonstrated that ZIKV could evade the cellular antiviral response by degrading STAT2 in human cells but not in mouse cells ^[2]. In this study, they found that stat2^-/- mice were highly susceptible to ZIKV infection. In addition, the authors used these stat2^-/- mice to investigate the pathogenesis caused by two different lineages of ZIKV. The survival rate shown that stat2^-/- mice challenged by African ZIKV strains all died after 6~8 days post-infection; however, there were only rare occasional death of mice challenged by Asian ZIKV strains. In addition, African ZIKV strains could induce sever neurological symptoms earlier than Asian ZIKV strains. Interestingly, they found that the viral RNA level was not responsible for the strain differences. Besides, they found that the cell infiltration, immune responses and inflammation in mice challenged with African lineages were higher than Asian lineages. Taken together, the inflammatory cytokines but not viral RNA level caused different degree of ZIKV virulence in two distinct ZIKV lineages. This study might be helpful for the researches of strain-specific change in their pathogenesis in the future.

References:

1.      Ramos da Silva S, Gao SJ. Zika virus: An update on epidemiology, pathology, molecular biology, and animal model. Journal of Medical Virology. 2016; 88(8):1291-6.

2.       Grant A, Ponia SS, Tripathi S, Balasubramaniam V, Miorin L, Sourisseau M, et al. Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling. Cell Host Microbe. 2016; 19(6):882-890.