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.

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.