Myeloid Cell Recruitment and Function in Pathogenesis and Latency
Edward S. Mocarski, Jr., Gabriele Hahn, Kirsten Lofgren White, Jiake Xu, Barry Slobedman, Laura Hertel, Shirley A. Aguirre, and Satoshi Noda
from: Cytomegaloviruses: Molecular Biology and Immunology (Edited by: Matthias J. Reddehase). Caister Academic Press, U.K. (2006)
Abstract
Cytomegaloviruses have an association with myelomonocytic cells during acute infection, where they control viral dissemination, and latency, where progenitors are important sites for life-long viral genome residence. Recent efforts to understand the control of dissemination by virus-encoded chemokines have shown that immature myelomonocytic cells are recruited from the bone marrow to sites of viral infection. Investigations in mice that are deficient in CCR2 and CCL2 (MCP-1), a chemokine system responsible for monocyte recruitment from blood into tissues, exhibit no differences in susceptibility or dissemination patterns, suggesting that late myeloid progenitors rather than more mature monocytes or monocyte-derived macrophages, play key roles in MCMV dissemination. This, paired with understanding of HCMV pathogenesis from studies in naturally infected individuals, suggests that cytomegaloviruses depend on myeloid cell progenitors for both acute infection and latency. Latent infection by HCMV in granulocyte-macrophage progenitors is accompanied by the expression of specific latency-associated transcripts from the IE1/IE2 region whose gene products have not yet been found to affect experimental latent infection. A portion of the IE1/IE2 transcriptional enhancer-modulator that is dispensable for productive replication is important for genome maintenance in latency, predicting that HCMV has an origin of DNA replication in this region read more ...
