Exploring the potential involvement of human macrophage and dendritic cells in the pathogenesis Zika virus

Dr Chu, Hin   (Principal Investigator (PI))

Dr Zhou Jie   (Co-Investigator)

12

2016-06-25

2017-06-24

150000

Exploring the potential involvement of human macrophage and dendritic cells in the pathogenesis Zika virus

Cell death, DC, MDM, Pro-inflammatory cytokine, Virus replication, Zika virus

Virology

201606159014

Seed Fund for Basic Research for New Staff

2015

Completed

Zika virus (ZIKV) is a flavivirus that is transmitted by mosquito vectors of the Aedes genus. The virus was initially isolated from a febrile rhesus macaque in the Zika Forest near Entebbe of Uganda in 1947 (Dick GW, 1952). The virus remained at a low profile between 1947 and 2006, which caused only ~14 human cases in Africa and Asia. The first notable outbreak of ZIKV among the human population occurred in Yap Island of the Federated States of Micronesia in 2007. In an investigation that aimed to define the epidemiologic features of the Yap Island ZIKV outbreak, blood samples from 414 out of 557 household residents had IgM antibody against ZIKV, suggesting that 74% of the population of the Yap Island was exposed to ZIKV infection (Duffy MR, 2009). Since then, ZIKV epidemic has expanded and spread to the western hemisphere including many Latin American countries. By the end of 2015, Brazil alone has reported 500,000 to 1.5 million estimated human cases of ZIKV infection (Bogoch II, 2016). Clinically, most patients infected with ZIKV are asymptomatic. The symptomatic patients predominantly develop mild symptoms including rash, fever, headache, conjunctivitis, and arthralgia (Duffy MR, 2009). The potential association between ZIKV infection and neurological complications was unveiled during the ZIKV outbreak in French Polynesia, during which the incidence of Guillain-Barre syndrome was increased by 20-fold (Oehler E, 2014). In the recent ZIKV outbreak in Brazil, increasing evidence suggests infection with ZIKV may have a causal association with the development of congenital neurological abnormalities including microcephaly (Hazin AN, 2016). Taken together, the rapidly expanding epidemic combined with the association between ZIKV and congenital neurological abnormalities have prompted the global community to recognize ZIKV as an imminent public health threat. To this end, the WHO declared the ZIKV outbreak as a global public health emergency on February 1st, 2016. Macrophage and dendritic cells are key sentinel cells of the immune system. Both cell types are responsible for recognizing, capturing, and presenting foreign antigens to naïve T cells. In addition, both cell types are critical cytokine production cells, which are capable of producing antiviral and inflammatory cytokine and chemokines for host defence. Despite the importance of macrophages and dendritic cells in the immune system, a large number of viruses have evolved strategies to hijack the cellular machinery of macrophages and dendritic cells to their own advantages. In the case of flavivirus infection, subsets of tissue macrophages and dendritic cells are among the first cell types that encounter the viruses. The dengue virus (DENV) can efficiently infect human macrophage and dendritic cells, using them as replication reservoirs, as well as vehicles of dissemination. In addition, DENV can suppress interferon production from dendritic cells, crippling their capacity in mounting an optimal anti-viral immune response. To date, only one study examined the susceptibility of dendritic cells to ZIKV infection (Hamel R, 2015). Important questions including whether ZIKV can replicate in macrophages and dendritic cells, whether ZIKV can suppress or induce interferon production in macrophages and dendritic cells, and whether ZIKV can induce apoptosis in macrophages and dendritic cells, remain completely unanswered. In this study, we will investigate the interaction between ZIKV and macrophages/dendritic cells. Information obtained from this study will contribute to the establishment of effective therapeutic regimens to combat the ZIKV epidemic.