Zika virus (ZIKV) is transmitted sexually and in utero, which leads to devastating birth defects in babies and is a unique feature amongst mosquito-borne viruses. Therapeutics or vaccines for preventing congenital ZIKV syndrome in infants are not available. Therefore, there is a critical need to identify the factors that decrease the risk of ZIKV infection in pregnant women in order to prevent congenital ZIKV syndrome. During the ZIKV pandemic, we established a human cohort of 185 ZIKV-infected men to study the sexual transmission potential of ZIKV. We found that shedding of ZIKV RNA in semen occurred in 50% of infected men, with infectious ZIKV detected in semen for 1-2 months post-onset of disease. Furthermore, in our mouse model of sexual transmission, which recapitulates the ZIKV replication kinetics in human semen, sexual transmission of ZIKV from infected males to females enhanced infection of the female reproductive tract and fetuses compared to intravaginal or subcutaneous exposure of females to ZIKV. Thus, we identified sexual transmission of ZIKV as a significant risk factor for ZIKV in utero transmission in pregnant women. We are now studying the effect of ZIKV sexual transmission on male reproductive tract health and vaginal susceptibility to ZIKV.
Usutu virus (USUV) is a mosquito-borne virus that is closely related to West Nile virus (WNV) and St. Louis Encephalitis virus (SLEV), both of which are enzootic in North America. USUV causes febrile illness and neuroinvasive disease in infected humans. USUV was previously restricted to Africa but has been detected in Europe since 2001 with increasing geographic range. USUV has primarily been detected in Culex mosquitoes and passerine birds (songbirds), similar to WNV and SLEV, though the host species that are critical for enzootic maintenance of the virus are unknown. Large-scale bird die-offs have accompanied the emergence of the virus in Europe, reminiscent of the introduction of WNV into the U.S. in 1999. We have found that USUV isolates differ significantly in pathogenesis using a mouse model, and we are now identifying the viral genetic determinants of USUV pathogenesis using a reverse genetics system developed by virologist Dr. James Weger-Lucarelli at Virginia Tech. We also established a bird model of USUV infection in collaboration with geneticist Dr. Paul Siegel at at Virginia Tech, and we are using this model to measure host competence for USUV.
Epidemiological studies suggest that emerging SARS-CoV-2 variants have increased transmission rates, indicating that SARS-CoV-2 may be evolving to accelerate transmission. SARS-CoV-2 vaccines are not yet sufficiently widely available to eliminate the global burden of disease and may be driving changes in the virus, necessitating a greater understanding of transmission mechanisms. Viruses are transmitted in respiratory particles (droplets and aerosols) that are emitted during coughing, sneezing, talking, and breathing. In collaboration with engineer Dr. Linsey Marr at Virginia Tech, we developed a novel model for collecting aerosol particles containing SARS-CoV-2 from hamsters. We are studying the viral, host, and environmental factors that impact SARS-CoV-2 emission.