The pathogenicity of cytomegalovirus

Abstract

Human cytomegalovirus is ubiquitous, yet causes little illness in immunocompetent individuals. Disease is evident in immunodeficient groups such as neonates, transplant recipients and AIDS patients either following a primary infection or reactivation of a latent infection. Little is known of the mechanisms underlying the pathogenicity of the virus. The recent determination of the nucleotide sequence of both human cytomegalovirus (strain AD169) and murine cytomegalovirus (murine cytomegalovirus strain Smith) has allowed an analysis of the biological importance of several virus genes. Studies with human cytomegalovirus have indicated that many viral genes are non-essential for replication in vitro which are thus assumed to be important in the pathogenesis of the virus. This is being examined in the murine model where the role of the gene and its product in disease can be directly examined in vivo using viral mutants in which the relevant gene has been interrupted or deleted. Current information on the role of cytomegalovirus genes in tissue tropism, immune evasion, latency, reactivation from latency and damage is described.

Simultaneous Reconstitution of Multiple Cytomegalovirus‐Specific CD8+Cell Populations with Divergent Functionality in Hematopoietic Stem‐Cell Transplant Recipients

“…However, the lower levels and/or slower expansion of IE-1-specific CD8 + T lymphocytes, compared with those of lymphocytes specific for pp65 and pp50-which were seen in all 3 of the HSCT recipients shown in figure 1-combined with the observed less-functional phenotype of IE-1-specific cells, suggests partial impairment of IE-1-specific responses. This IE-1-specific difference could be explained by the effect of different in vivo host cells on the effectiveness of viral immunoevasion strategies [41,42]. How this might happen has been shown by in vitro experiments that have reported the escape from inhibition of IE-1 peptide presentation by macrophages [43], compared with the tight control of IE-1 antigen presentation in fibroblasts [44].…”

Impact of Local Endothelial Challenge with Cytomegalovirus or Glycoprotein B on Vasodilation in Intact Pressurized Arteries from Nonpregnant and Pregnant Mice1

“…Active or reactivated HCMV infections may affect the vasculature during times of stress [2], immune suppression [3], and/or pregnancy [4]. HCMV is associated with several vascular diseases, including atherosclerosis, coronary heart disease, and vasculopathy [5][6][7]. During pregnancy, HCMV infections have also been associated with the hypertensive disorder preeclampsia [7][8][9].…”

Engineering of cytomegalovirus genomes for recombinant live herpesvirus vaccines

“…There are analogies in the pathogenesis of CMV infection in mice and humans, as indicated by similar clinical manifestations, occurrence of latency or sensitivity to antiviral drugs. Especially the use of immunocompromised mice allows the extensive study of clinical conditions for CMV infections (Baskar et al, 1983;Li and Tsutsui, 2000;Reddehase et al, 2002;Shanley et al, 1985;Sweet, 1999;Tsutsui, 1995).…”