Horizontal transmission of a murine retrovirus is driven by males within semi-natural enclosures

1. Transmission is a key component of a pathogen’s life history, but it is often difficult to obtain reliable ecological estimates of the dominant mode(s) of transmission and how host traits, such as sex, influence transmission dynamics. 2. Here, we have developed a robust system pairing the use of semi-natural populations of house mice (Mus musculus) with modern molecular viral titering approaches to evaluate the transmission dynamics of Friend Virus Complex (FVC). 3. Semi-natural populations were founded with female and male mice that were either ‘index’ (initially infected via intraperitoneal injection) or ‘contact’ (uninfected at the start of experiment). Three experimental population designs were implemented: female index only, male index only, and both female and male index. 4. Utilizing these enclosures, we found male-male transmission to be the predominant mode of transmission, with low rates of horizontal female transmission and no evidence of vertical transmission. Additionally, contact males that became infected harbor higher titers than females, while suffering a similar amount of spleen enlargement; this, paired with a strong correlation between titer and spleen size in males, and no correlation in females, indicates FVC viral dynamics differ between the sexes. 5. Lastly, natural transmission may be an impediment to FVC replication as infected contact animals have a lower viral titer than index animals. These results illuminate the complex life history of murine leukemia viruses and demonstrate the important role of host sex on pathogen transmission dynamics.