The environment is a key factor in the outcome of virus-host interactions, eventually modulating the infection outcome and its severity. Indeed, it has been shown in different organisms that microgravity affects their immunity (Ryba-White et al., 2001; Gilbert et al., 2020; Zhu et al., 2021). Therefore, future long-term space missions will need to consider the potential effects of microgravity on the course of possible infections affecting the astronauts, as well as the extent in which the associated changes in host physiology might impact the pathogen evolution and virulence. In this proposal we suggest to use the nematode Caenorhabditis elegans, an organism already being used in space research (Liu et al., 2019), as a host to study the effects that microgravity may have in the progression of viral infections. C. elegans is a millimetric nematode with a short lifecycle with most of their genes having homologs with human genes, which makes it an ideal system to study pathogenesis as the results can be extrapolated to humans or other animal hosts. The discovery of the first virus naturally infecting C. elegans (Orsay nodavirus, OrV) has made the nematode an emergent model in the study of virus infection and immunity (Félix et al., 2011). It is known that simulated microgravity conditions (SMC) induces intestinal damage in C. elegans (Liu et al., 2019) and that OrV replicates in the intestinal cells of the nematode (Franz et al., 2014). Therefore, it seems conceivable that microgravity will have an effect on the progression of OrV infection. This would have relevant consequences on the virus pathogenesis, conditioning infection outcomes and virulence evolution. In summary, the goals of the project are: (a) to characterize viral infections under microgravity conditions; (b) to identify the response mechanisms of a host under microgravity conditions upon viral infections; (c) to evaluate how microgravity affects the evolution of virus’ virulence.