TMEM41B is a pan-flavivirus host factor (preprint)

SUMMARY Flaviviruses pose a constant threat to human health. These RNA viruses are transmitted by the bite of infected mosquitoes and ticks and regularly cause outbreaks. To identify host factors required for flavivirus infection we performed full-genome loss of function CRISPR-Cas9 screens. Based on these results we focused our efforts on characterizing the roles that TMEM41B and VMP1 play in the virus replication cycle. Our mechanistic studies on TMEM41B revealed that all members of the Flaviviridae family that we tested require TMEM41B. We tested 12 additional virus families and found that SARS-CoV-2 of the Coronaviridae also required TMEM41B for infection. Remarkably, single nucleotide polymorphisms (SNPs) present at nearly twenty percent in East Asian populations reduce flavivirus infection. Based on our mechanistic studies we hypothesize that TMEM41B is recruited to flavivirus RNA replication complexes to facilitate membrane curvature, which creates a protected environment for viral genome replication. HIGHLIGHTS TMEM41B and VMP1 are required for both autophagy and flavivirus infection, however, autophagy is not required for flavivirus infection. TMEM41B associates with viral proteins and likely facilitates membrane remodeling to establish viral RNA replication complexes. TMEM41B single nucleotide polymorphisms (SNPs) present at nearly twenty percent in East Asian populations reduce flavivirus infection. TMEM41B-deficient cells display an exaggerated innate immune response upon high multiplicity flavivirus infection.

COVID-19 and Alleged Child Maltreatment (preprint)

The policy response to the COVID-19 pandemic led to a sudden and unprecedented increase in the amount of time parents and children spent at home. We use real-time, novel mobile phone movement data and quick-release administrative data on child maltreatment referrals to examine how time at home is related to allegations of child maltreatment. Findings show that allegations plummeted by approximately 55% following the emergency declaration relative to 2018 and 2019 trends during the same time period. However, time at home during the pandemic was associated with more referrals, particularly of supervisory neglect, with the largest impacts in metropolitan counties, counties with historically lower referral rates, and counties with more poverty. We also find that more time at home is positively related to educational neglect referrals among children in areas with high poverty and higher referral rates. Our results highlight how children and families are faring during the pandemic, and we offer several clinical and policy implications.