Prior Infection with Torque Teno Virus Mitigates Influenza Pathology in Mice

Respiratory infections caused by influenza viruses are frequently associated with coinfection by other infectious agents. Torque teno viruses (TTVs) are small DNA viruses that can function as opportunistic pathogens and are epidemiologically linked to influenza viruses as well as a broad spectrum of infectious and immune-mediated diseases. Among TTVs, swine torque teno viruses (TTSuVs) are unique in that they have been shown to act as primary pathogens. With the long-term objective of developing experimental tools to better understand inter-viral interactions, this study aimed to optimize a murine model of TTV and influenza virus coinfection. Experimental mice were inoculated with TTSuV1 on day 1 post infection (DPI 1), while phosphate-buffered saline (PBS)-treated mice served as negative controls. A subset of TTSuV1-infected mice was subsequently coinfected with the influenza A virus H1N1 (IAV) at either 12 or 27 days following TTSuV1 infection. An additional group of mice was maintained as an IAV only control. Mice infected with IAV were euthanized 72-84 h post-IAV infection, corresponding to DPI 15 and 30, respectively. Unexpectedly, gross and histopathological examination of lung tissues revealed that prior TTSuV1 infection significantly attenuated IAV-induced pathology in coinfected mice. Coinfected animals also exhibited a tendency toward reduced IAV replication in the lungs as measured by qPCR, TCID₅₀ and HAs compared to mice infected with IAV alone, accompanied by lower levels of virus-specific antibodies to IAV at DPI 30 and TTSuV1 at DPI 15 respectively. At DPI 30, TTSuV1 genomic DNA levels in lung tissue and whole blood were higher in coinfected mice, suggestive of prolonged viremia in the coinfected group. Collectively, these findings establish baseline parameters for a murine TTV and influenza coinfection model and provide a foundation for future studies aimed at elucidating the molecular and immunological mechanisms underlying viral coinfections.