ZIKA VIRUS PATHOGENESIS AT SITES OF VECTOR-INDEPENDENT TRANSMISSION AND A FORAY INTO APPLIED SEROPREVALENCE

Abstract

Zika virus (ZIKV) recently emerged in 2016 spread by mosquito-borne, sexual, and congenital transmission. During the course of this work, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also emerged and has been one of the most significant causes of mortality in 2020 as a result of the disease it causes, coronavirus disease 2019 (COVID-19). Because ZIKV causes placental damage, I set out to establish in collaboration with Tulika Singh in Dr. Sallie Permar’s laboratory whether antibody transfer is preserved during gestational ZIKV infection. I found that approximately half of our small 20-person cohort had serologic evidence of ZIKV infection during gestation and that ZIKV infection does not impair transfer of ZIKV and DENV-neutralizing antibodies. One individual had prolonged infection during gestation, and I showed that an IgM isolated from this individual potently neutralizes ZIKV and can protect mice from severe disease. I also investigated ZIKV replication in the vagina of wild-type (WT) mice. Typically, ZIKV infections in the laboratory are performed in mice deficient in IFN-αβ signaling because these mice are permissive to disseminated infection following inoculation by footpad. I found that ZIKV infection in the vagina is regulated by progesterone but not IFN-αβ signaling. I also found that progesterone-induced susceptibility to ZIKV is unlikely to be due to decreased epithelial integrity, changes in leukocyte numbers in vaginal tissue, or dampened antiviral signaling in the vagina. Finally, I coordinated a multi-site effort to measure SARS-CoV-2 seroprevalence over a 6-month time frame. We found that Latinx and underinsured individuals were at greatest risk of infection. Also, SARS-CoV-2 neutralizing antibody titers for individuals without respiratory symptoms were lower than for those with symptoms or COVID-19 diagnosis, supporting that asymptomatic infections may result in lower neutralizing titers.My results support that transplacental antibody transfer is not solely a result of placental damage. They also support that progesterone regulates some aspect of viral susceptibility independent of the interferon response. My results also emphasize that those at risk of systemic racism also may be at greatest risk of infection of emerging viruses that are driven by transmission in close quarters.Doctor of Philosoph