HCMV infection is common; 60% of the UK population have experienced infection by the age of 40. Most infections are asymptomatic. Apart from during pregnancy and newborn infants exposed in utero, active (as opposed to latent) HCMV infection only occurs in people with immune defects, specifically T-cell defects, e.g. AIDS patients and immunosuppressed transplant patients.
Transmission is believed to be by oral/respiratory route. Infection produces enlargement of cells and nuclear inclusion bodies in a wide range of tissues - systemic infection.
Healthy HCMV seropositive blood donors can sometimes transmit HCMV infection to recipients. The risk of transmission by blood is reduced by using leukocyte depleted blood products, suggesting that one site of carriage of this virus is in the peripheral blood compartment. However, it is difficult, if not impossible, to isolate HCMV directly from the blood of healthy donors. Consequently, while peripheral blood of healthy seropositive individuals does not carry infectious virus, the virus must be in a form that is reactivatable. Using PCR, a number of laboratories have demonstrated the presence of HCMV DNA and/or RNA in the blood of seropositive individuals. Such analyses suggest that the frequency of cells that carry the HCMV genome is extremely low (probably less than 1 in 10,000 PBMC) and it is perhaps for this reason that other laboratories have been unable to detect HCMV DNA in the blood of healthy carriers. Monocytes appear to be the major site of carriage of HCMV DNA in healthy carriers with little viral DNA detectable in T or B cells. In vitro, long-term culture of peripheral blood monocytes towards a macrophage phenotype results in a cell population that is permissive for HCMV. Thus there is a link between the state of differentiation of myeloid cells and their permissiveness for HCMV infection. As with all lymphoid and myeloid cells, monocytes arise from pleuripotent CD34+ stem cells present in bone marrow. These cells can be infected with clinical isolates of HCMV, but little or no viral lytic gene expression occurs until they have been cultured long term in the presence of haemopoetic growth factors (e.g. GM-CSF). Bone marrow does appear to act as a reservoir for HCMV in vivo.
However, little or no viral gene expression is detectable in blood of healthy carriers. HCMV lytic gene expression (IE genes) is absent in monocytes, consistent with the inability to culture virus from these cells. Consequently, it would appear that HCMV is carried in a true latent state with little or no accompanying lytic gene expression.
Compared with HSV, relatively little is known about latency in HCMV. However, there may be a novel promoter slightly upstream of the major IE promoter/enhancer which generates novel spliced and unspliced RNA transcripts mapping to both strands of the HCMV major IE region, which may be functionally equivalent to HSV latency associated transcripts (LATs) or EBV EBNAs.
Cytomegalovirus escapes Natural Killer cells through HLA-E upregulation (Tomasec P. et al. Science 287, 1031, 2000).
In spite of the widespread distribution, HCMV-related illness is rare and occurs only in two groups:
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Mr Campbell's Kidney |
Activation of latent HCMV (common) to a lytic state of infection (rarer) therefore appears to require one (or both) of two conditions: