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.

Intracellular Retention of the MHC Class I-Related Chain B Ligand of NKG2D by the Human Cytomegalovirus UL16 Glycoprotein

“…Human CMV persists lifelong in a latent state with asymptomatic episodes of virus shedding. Only in immunocompromised individuals, virus reactivation results in severe disease manifestations (3,4). To maintain longterm persistence in infected hosts, CMV interferes with several stages of Ag processing and presentation by MHC class I molecules, thus compromising the ability of CD8 ␣␤ T cells to eliminate infected cells.…”

Molecular Mechanism and Structural Aspects of Transporter Associated with Antigen Processing Inhibition by the Cytomegalovirus Protein US6

“…In immunocompromised individuals like recipients of organ transplants, AIDS patients, and infants in utero, HCMV infection may cause fatal disease (for review see Ref. 13). The ER-resident type I transmembrane glycoprotein US6 has been identified to block TAP function and therefore helps infected cells to evade host immunity (14 -16).…”

Evaluation of an in-house specific immunoglobulin G (IgG) avidity ELISA for distinguishing recent primary from long-term human cytomegalovirus (HCMV) infection

“…HCMV is a serious, life-threatening opportunistic pathogen in immunocompromised persons, and is one of the principal causes of congenital malformations and neurological defects in infected neonates [19][20][21][22] .…”

“…Although HCMV has a world-wide distribution, infection with HCMV is more common in developing countries, particularly in areas with poor socioeconomic conditions 5,22 . As with other herpesvirus infections, primary HCMV infection is followed by chronic infection or viral latency from which the virus may be reactivated 21 . Primary infection or reactivation of HCMV is usually either subclinical or self-limiting in immunocompetent persons 5,12,18 .…”

“…Primary infection or reactivation of HCMV is usually either subclinical or self-limiting in immunocompetent persons 5,12,18 . However, in immunocompromised hosts such as organ transplant recipients, patients with cancer and individuals infected with human immunodeficiency virus (HIV), or in congenital infections, a significantly adverse clinical course and outcome is often seen [18][19][20][21][22] .…”