For these reasons, in this work, we performed a comprehensive functional characterization of Envs from these LTNP-EC viruses, focusing on the initial events of viral infection: binding of Env to CD4+ cells, Env-triggered early signals for actin and α-tubulin cytoskeleton modulation, and the subsequent membrane fusion and early infection in target cells. This evidence concerns the gene ERVW-1 and viral infectious disease.