Project description:Novel coronavirus causing Covid-19 identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused pandemic in 2020. Although the virus and disease in humans has been thoroughly researched, so far there has not been animal model comparable to humans – genetically diverse species able to get infected and sick from Covid-19. The white-footed deermouse Peromyscus leucopus is a long-lived rodent and a key reservoir in North America for agents of several zoonoses including Lyme disease, babesiosis, anaplasmosis, and viral encephalitis. While persistently infected, this deermouse avoids apparent disability or diminished fitness. Its tolerance to infection with sometimes more than one pathogen makes P. leucopus comparable to bats. This study uses P. leucopus, LL colony stock, as a genetically diverse animal model for viral infection with SARS-CoV-2. We infected P. leucopus with SARS-CoV-2, collected plasma, lungs, and brain 3 and 6 days post-infection, and compared to control animals. P. leucopus mount an immune response against viral pathogens through production of neutralizing antibodies and genome-wide transcription of type I interferon stimulated genes in lungs compared to naïve animals. Viral RNA detection correlates with gene expression of type I interferon stimulated genes in response to viral infection in the brain. We report that diversity of outbred animals, their sex and age is reflected in the range of responses. These results show that P. leucopus is a viable animal model for SARS-CoV-2, particularly in research of viral infection of the brain.
Project description:Novel coronavirus causing Covid-19 identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused pandemic in 2020. Although the virus and disease in humans has been thoroughly researched, so far there has not been animal model comparable to humans – genetically diverse species able to get infected and sick from Covid-19. The white-footed deermouse Peromyscus leucopus is a long-lived rodent and a key reservoir in North America for agents of several zoonoses including Lyme disease, babesiosis, anaplasmosis, and viral encephalitis. While persistently infected, this deermouse avoids apparent disability or diminished fitness. Its tolerance to infection with sometimes more than one pathogen makes P. leucopus comparable to bats. This study uses P. leucopus, LL colony stock, as a genetically diverse animal model for viral infection with SARS-CoV-2. We infected P. leucopus with SARS-CoV-2, collected plasma, lungs, and brain 3 and 6 days post-infection, and compared to control animals. P. leucopus mount an immune response against viral pathogens through production of neutralizing antibodies and genome-wide transcription of type I interferon stimulated genes in lungs compared to naïve animals. Viral RNA detection correlates with gene expression of type I interferon stimulated genes in response to viral infection in the brain. We report that diversity of outbred animals, their sex and age is reflected in the range of responses. These results show that P. leucopus is a viable animal model for SARS-CoV-2, particularly in research of viral infection of the brain.
Project description:The Lyme disease spirochete Borrelia burgdorferi drives a range of acute and chronic maladies in humans and other incidental hosts infected with the pathogen. However, the primary vertebrate reservoir, Peromyscus leucopus appears spared from any symptomology following infection. This has led to a common hypothesis that P. leucopus and B. burgdorferi exist symbiotically: P. leucopus restrain their immune response against the microbe and enable the enzootic cycle while B. burgdorferi avoids causing damage to the host. While aspects of this hypothesis have been tested, the exact interactions that occur between P. leucopus and B. burgdorferi during infection remain largely unknown. Here we utilized an inbred colony of P. leucopus in order to compare B. burgdorferi (B31) fitness in these rodents to the traditional B. burgdorferi murine models—C57BL/6J and C3H/HeN Mus musculus, which develop signs of inflammation akin to human disease. We find that in contrast to our expectations, B. burgdorferi were able to reach much higher burdens in M. musculus, and that the overall kinetics of infection differed between the two rodent species. Surprisingly, we also found that P. leucopus remained infectious to larval Ixodes scapularis for a far shorter period than either M. musculus strain. In line with these observations, we found that P. leucopus does launch a modest but sustained inflammatory response against B. burgdorferi in the skin, which we hypothesize leads to reduced bacterial viability and infectivity in these hosts. These observations provide new insight into the nature of reservoir species and the B. burgdorferi enzootic cycle.