Murine cytomegalovirus displays selective infection of cells within hours after systemic administration

Kimberly M. Hsu, Jennifer R. Pratt, Walter J. Akers, Samuel I. Achilefu, Wayne M. Yokoyama

Research output: Contribution to journalArticle

73 Scopus citations

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.

Original languageEnglish
Pages (from-to)33-43
Number of pages11
JournalJournal of General Virology
Volume90
Issue number1
DOIs
StatePublished - Apr 27 2009

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