Grant: Team Grant: Canada-Latin/America-Caribbean Zika Virus Program - Pathogenesis

Zika virus (ZIKV) is an emerging mosquito-transmitted human pathogen of great cause of concern in the Americas and has been declared a global public health emergency by the world health organization. Over fifty countries are affected with more than 2 million infections and over 4,000 suspected cases of ZIKV-related birth defects in Brazil. Unfortunately, there are no antivirals or vaccines currently available against the virus. The Aedes species (A. aegypti and A. albopictus) of mosquitoes are mainly responsible for the transmission, however, multiple cases of sexual transmission have also been reported. In the majority of cases, infection is asymptomatic or results in mild self-limiting disease with symptoms including maculopapular rash, low grade fever, headache and body aches lasting up to a week. The unprecedented rise in birth defects including microcephaly (abnormal smallness of the head) in ZIKV affected areas in Brazil raised the urgency for understanding the molecular mechanisms governing infection and transmission. It is now established that ZIKV can infect placental cells and remain persistent in fetal tissues. Thus, there is a strong causal relationship between maternal ZIKV infection and microcephaly and fetal brain anomalies. Interestingly, infectious ZIKV has been recovered from the semen of infected males long after acute symptoms had resolved and the testes demonstrated the highest viral replication (higher than the brain) in two separate mouse models. Other flaviviruses such as DENV, are not associated with birth defects or sexual transmission. Through understanding how ZIKV manipulates host cells during acute and persistent infections, it may be possible to develop anti-viral therapies against this important pathogen.