Distribution of Mouse Adenovirus Type 1 in Intraperitoneally and Intranasally Infected Adult Outbred Mice

Abstract

In situ nucleic acid hybridization and immunohistochemistry were used to determine the histological localization of mouse adenovirus type 1 (MAV-1) during acute infection of adult mice infected either intraperitoneally or intranasally with 1,000 PFU of wild-type virus. Organ samples were collected from days 1 to 17 postinfection for the intraperitoneally infected mice and from days 1 to 13 for the intranasally infected mice. Endothelial cells of the brain and spinal cord showed extensive evidence of MAV-1 infection. Endothelial cells in lungs, kidneys, and other organs were also positive for MAV-1, indicating a widespread involvement of the systemic circulation. The presence of viral nucleic acid and/or antigen was also demonstrated in lymphoid tissue. The spleens, Peyer’s patches, and peripheral lymph nodes showed positive staining at various times postinfection in mice infected by either route. Virus-infected cells in the spleen exhibited a stellate shape and were localized to the red pulp and germinal centers, suggesting that they are cells of the mononuclear phagocytic system.

Xenogenic Adenoviral Vectors

“…177,178 Unlike HAdVs, which initially infect the respiratory epithelium, MAdV-1 replicates in the primary endothelial cells of various body systems and thus results in widespread systemic infection affecting the liver, spleen, kidneys, intestines, adrenals, heart, brain, and spinal cord. 179,180 The genome of MAdV-1 is ∼30.9 kbp and is similar to HAdV-5 in organization except that it does not encode virus-associated RNAs. 181,182 Vectors based on MAdV-1 were first described in the late 1990s.…”

Mouse adenovirus type 1 infection of macrophages

“…We previously showed that MAV-1-specific nucleic acid is detectable by in situ hybridization in macrophages of outbred Swiss mice (Kajon et al, 1998). To determine whether the virus replicates in monocytes, we performed ex vivo infections of bone marrow-derived macrophages and DCs.…”

“…To understand how MAV-1 disseminates and causes disease in immunocompetent and immunodeficient mice, it is important to know the cell types it infects and how infection affects their normal cell function. MAV-1 targets endothelial cells throughout the mouse, with the highest levels of virus being found in the brain, spinal cord, and spleen (Charles et al, 1998;Guida et al, 1995;Kajon et al, 1998;Kring et al, 1995;Moore et al, 2003). Cells of the monocyte lineage are potentially targets of infection by MAV-1, but their infection by MAV-1 has not been well studied previously.…”

“…Cells of the monocyte lineage are potentially targets of infection by MAV-1, but their infection by MAV-1 has not been well studied previously. MAV-1 early region 3 (E3) nucleic acid was detected by in situ hybridization in cells histologically identified as macrophages (Kajon et al, 1998). MAV-1 E3 antigen was reported to be detected in Kupffer cells of MAV-1-infected mice (Lenaerts et al, 2005).…”

Xenogenic Adenoviral Vectors

“…Few studies on the biodistribution and persistence of xenogenic AdVs in vivo have been reported, but some have been carried out with MAdVl and OAdV7. In the homologous situation, mice were injected intraperitoneally (ip) or intranasally with 10^ pfu of MAdVl and the localization of virus was monitored histologically during acute infection [152]. Endothelial cells of the brain and spinal cord showed extensive evidence of infection.…”