Biology and Cellular Tropism of a Unique Astrovirus Strain: Murine Astrovirus 2

• Published in: Comparative medicine Vol. 71; no. 6; pp. 474 - 484
• Main Authors: Kelly, Sean P, Ricart Arbona, Rodolfo J, Michel, Adam O, Wang, Chuanwu, Henderson, Kenneth S, Lipman, Neil S
• Format: Journal Article
• Language: English
• Published: United States American Association for Laboratory Animal Science 01.12.2021
• Subjects: Animals; Astroviridae; Biology; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Original Research; Tropism
• ISSN: 1532-0820
• DOI: 10.30802/AALAS-CM-21-000039

Murine astrovirus 2 (MuAstV2) is a novel murine astrovirus recently identified in laboratory and wild mice. MuAstV2readily transmits between immunocompetent mice yet fails to transmit to highly immunocompromised mouse strains—a unique characteristic when contrasted with other murine viruses including other astroviruses. We characterized the viralshedding kinetics and tissue tropism of MuAstV2 in immunocompetent C57BL/6NCrl mice and evaluated the apparentresistance of highly immunocompromised NOD Prkdcem26Cd52Il2rgem26Cd22/NjuCrl mice to MuAstV2 after oral inoculation. Temporal patterns of viral shedding were determined by serially measuring fecal viral RNA. Tissue tropism and viral load were characterized and quantified by using in-situ hybridization (ISH) targeting viral RNA. Cellular tropism was characterized by evaluating fluorescent colocalization of viral ISH with various immunohistochemical markers. We found a rapidincrease of fecal viral RNA in B6 mice, which peaked at 5 d after inoculation (dpi) followed by cessation of shedding by 168dpi. The small intestine had the highest percentage of hybridization (3.09% of tissue area) of all tissues in which hybridization occurred at 5 dpi. The thymus displayed the next highest degree of hybridization (2.3%) at 7 dpi, indicating extraintestinal viral spread. MuAstV2 RNA hybridization was found to colocalize with only 3 of the markers evaluated: CD3 (T cells), Iba1 (macrophages), and cytokeratin (enterocytes). A higher percentage of CD3 cells and Iba1 cells hybridized with MuAstV2 as compared with cytokeratin at 2 dpi (CD3, 59%; Iba1, 46%; cytokeratin, 6%) and 35 dpi (CD3, 14%; Iba1, 55%; cytokeratin, 3%). Neither fecal viral RNA nor viral hybridization was noted in NCG mice at the time points examined. In addition, mice of mixed genetic background were inoculated, and only those with a functioning Il2rg gene shed MuAstV2. Results from this study suggest that infection of, or interaction with, the immune system is required for infection by or replication of MuAstV2.