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Multiple viruses that are highly pathogenic in humans are known to have evolved in bats. How bats tolerate infection with these viruses, however, is poorly understood. As viruses engage in a wide range of interactions with their hosts, it is essential to study bat viruses in a system that resembles their natural environment like bat-derived in vitro cellular models. However, stable and accessible bat cell lines are not widely available for the broader scientific community. Here, we generated in vitro reagents for the Seba’s short-tailed bat (Carollia perspicillata), tested multiple methods of immortalization, and characterized their susceptibility to virus infection and response to immune stimulation. Using pseudotyped virus library and authentic virus infections, we show that theseC. perspicillatacell lines derived from a diverse array of tissues are susceptible to viruses bearing the glycoprotein of numerous orthohantaviruses, including Andes and Hantaan virus and are also susceptible to live hantavirus infection. Furthermore, stimulation with synthetic double-stranded RNA prior to infection with vesicular stomatitis virus and Middle Eastern respiratory syndrome coronavirus induced a protective antiviral response, demonstrating the suitability of our cell lines to study the bat antiviral immune response. Taken together, the approaches outlined here will inform future efforts to develop in vitro tools for virology from non-model organisms and theseC. perspicillatacell lines will enable studies on virus–host interactions in these bats. 

ABSTRACT Accumulating data suggest that some bat species host emerging viruses that are highly pathogenic in humans and agricultural animals. Laboratory-based studies have highlighted important adaptations in bat immune systems that allow them to better tolerate viral infections compared to humans. Simultaneously, ecological studies have discovered critical extrinsic factors, such as nutritional stress, that correlate with virus shedding in wild-caught bats. Despite some progress in independently understanding the role of bats as reservoirs of emerging viruses, there remains a significant gap in the molecular understanding of factors that drive virus spillover from bats. Driven by a collective goal of bridging the gap between the fields of bat virology, immunology, and disease ecology, we hosted a satellite symposium at the 2024 American Society for Virology meeting. Bringing together virologists, immunologists, and disease ecologists, we discussed the intrinsic and extrinsic factors such as virus receptor engagement, adaptive immunity, and virus ecology that influence spillover from bat hosts. This article summarizes the topics discussed during the symposium and emphasizes the need for interdisciplinary collaborations and resource sharing. 

The greatest challenge to preventing the next influenza pandemic is the extensive diversity within the influenza virus family ( 1 ). At present, 20 lineages of influenza A and B viruses have been identified, each containing numerous strains ( 2 , 3 ). Current influenza vaccines, composed of four influenza viral antigens, provide little protection beyond the viral strains targeted by the vaccines. Universal influenza vaccines that can protect against all 20 lineages could help to prevent the next pandemic ( 4 ). Designing and manufacturing a vaccine that can provide such broad protection has been challenging, but the demonstration of the feasibility of mRNA–lipid nanoparticle COVID-19 vaccines offers a possible strategy ( 5 ). On page 899 of this issue, Arevalo et al. ( 6 ) report an influenza vaccine, using mRNA–lipid nanoparticle technology incorporating representatives of all 20 influenza virus lineages, that protected mice and ferrets from diverse influenza viruses. This provides a pathway to a universal influenza vaccine. 

Individuals infected with the SARS-CoV-2 virus present with a wide variety of symptoms ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe response to COVID-19. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the genetic predisposition to severe COVID-19 outcomes. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform a locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify four introgressed alleles that are strong functional candidates for driving the association between this locus and severe COVID-19. Using reporter assays in the presence/absence of SARS-CoV-2 , we find evidence that these variants respond to viral infection. These variants likely drive the locus’ impact on severity by modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5 . These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes.