Male Syrian hamsters are more susceptible to intravenous infection with species C human adenoviruses than are females

Highlights: • After intravenous injection, HAdV-C replicated more in male hamsters than in females. • Hepatocytes of male hamsters were infected more with HAdV-C than those of females. • This enhanced infection and replication resulted in more pathology. • There was no difference between the sexes after intranasal infection with HAdV-C. Recently, increasing attention has been focused on the influence of sex on the course of infectious diseases. Thus far, the best-documented examples point toward an immune-mediated mechanism: the generally stronger immune response in females can result in a faster clearance of the pathogen or, conversely, a more severe immune-mediated pathology. Here, we report that human species C adenoviruses replicate more and cause more pathology in male Syrian hamsters than in females. We also show that this sex disparity is not caused by a stronger immune response to the infection by the female hamsters. Rather, the liver of male hamsters is more susceptible to adenovirus infection: after intravenous injection, more hepatocytes become infected in male animals than in females. We hypothesize that Kupffer cells (hepatic tissue macrophages) of female animals are more active in sequestering circulating virions, and thus protect hepatocytes more efficiently than those of males.