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Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
Murine cytomegalovirus displays selective infection of cells within hours after systemic administration
Kimberly M Hsu1, Jennifer R Pratt, Walter J Akers
1Howard Hughes Medical Institute, Division of Rheumatology, Washington University School of Medicine, St Louis, MO 63110, USA.
Abstract:
A distinctive feature of the cytomegaloviruses is their wide tissue tropism, demonstrated by the infection of many organs and cell types in an active infection. However, in experimental models of systemic infection, the earliest stages of infection are not well characterized, and it is unclear whether only certain cells are initially infected. Using a recombinant murine cytomegalovirus (MCMV) expressing green fluorescent protein (GFP), we tracked viral infection after systemic administration via intraperitoneal injection and showed that specific cells are infected within the first hours. We provide evidence that MCMV traffics as free virus from the peritoneal cavity into the mediastinal lymphatics, providing access to the bloodstream. We demonstrate that MCMV productively infected CD169(+) subcapsular sinus macrophages in the mediastinal lymph nodes, ER-TR7(+) CD29(+) reticular fibroblasts in the spleen and hepatocytes. Infection in the spleen followed a distinctive pattern, beginning in the marginal zone at 6 h and spreading into the red pulp by 17 h. By 48 h after infection, there was widespread infection in the spleen and liver with degeneration of infected cells. In addition, infected dendritic cells appeared in the white pulp of the spleen at 48 h post-infection. On the other hand, cowpox virus showed a different pattern of infectivity in the spleen and liver. Thus, early MCMV infection produces a distinct pattern of infection of selective cells.
Insights
Murine cytomegalovirus (MCMV) infection begins in specific cells like macrophages and fibroblasts within hours of systemic exposure. This early tropism influences the initial spread and pattern of MCMV infection in lymphoid organs and the liver.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Cytomegaloviruses exhibit broad tissue tropism during active infection.
- Early stages of systemic viral infection and initial cellular targets remain poorly understood.
- Experimental models are crucial for characterizing the initial events of viral spread.
Purpose of the Study:
- To investigate the earliest cellular targets and tissue tropism of murine cytomegalovirus (MCMV) following systemic infection.
- To elucidate the initial route of MCMV dissemination from the peritoneal cavity to systemic circulation.
- To characterize the temporal and spatial pattern of MCMV infection in lymphoid organs and the liver.
Main Methods:
- Utilized a recombinant MCMV expressing green fluorescent protein (GFP) for in vivo tracking.
- Administered MCMV intraperitoneally to mice to model systemic infection.
- Analyzed infected cell populations and viral distribution in lymph nodes, spleen, and liver at various time points post-infection.
Main Results:
- MCMV rapidly disseminates from the peritoneal cavity via mediastinal lymphatics into the bloodstream.
- Initial MCMV infection targets specific cells: CD169(+) macrophages in lymph nodes, ER-TR7(+) CD29(+) fibroblasts in the spleen, and hepatocytes.
- Spleen infection progresses from the marginal zone to the red pulp within 17 hours, with widespread infection and cell degeneration by 48 hours.
Conclusions:
- Early MCMV infection demonstrates a distinct tropism for specific cell types, including macrophages, fibroblasts, and hepatocytes.
- The initial route of MCMV spread involves lymphatic transport and subsequent infection of key immune and parenchymal cells.
- Understanding these early events is critical for comprehending MCMV pathogenesis and host responses.

