Cytomegalovirus Infections in Humans


Cytomegalovirus (CMV) is a herpes virus that causes severe disease in the immunocompromised because virus replication is normally held in check by cell‐mediated immune responses in patients with past infection. Patients receiving immunosuppressive drugs to allow allo‐transplantation, patients with AIDS (acquired immunodeficiency syndrome) or foetuses with immature immune responses are therefore at risk of developing CMV end‐organ disease. A high viral load is required for CMV end‐organ disease to develop. Ganciclovir is a potent inhibitor of CMV replication and can be used either for prophylaxis or for pre‐emptive therapy (administering the drug when CMV is detected in the blood). Both of these strategies effectively control CMV end‐organ disease in transplant patients. Three new drugs have recently completed phase II clinical trials (maribavir, brincidofovir and letermovir). Phase II studies of prototype CMV vaccines have recently published encouraging results, suggesting that CMV infection may ultimately be preventable by means of universal immunisation.

Key Concepts

  • CMV viraemia precedes CMV end‐organ disease.

  • Prompt treatment of CMV viraemia prevents end‐organ disease.

  • The probability of end‐organ disease is non‐linear with respect to viral load.

  • This threshold relationship is seen also in babies with congenital CMV infection and hearing loss.

  • Prompt treatment of congenital CMV infection can reduce the risk of progressive hearing loss.

  • Quantitative viraemia biomarkers can be used to assess the potency of antiviral drugs in humans.

  • These same biomarkers can be used to determine if vaccine given pre‐transplant can help control CMV replication post‐transplant.

  • Although clinically silent, CMV infection is associated with excess mortality in the general public.

  • Universal immunisation has the potential to provide health benefits greater than appreciated at present.

Keywords: cytomegalovirus; viral load; threshold; dynamics; indirect effects

Figure 1. Intracellular pathways leading to presentation of cytomegalovirus (CMV) peptide epitopes at the plasma membrane by HLA class I molecules. ER, endoplasmic reticulum; PM, plasma membrane; PRO, proteasome; RIB, ribosome; TAP, transporter associated with antigen presentation; TGN, trans‐Golgi network and V, virus‐encoded protein. Letters and numbers indicate CMV proteins that can interfere with antigen presentation (as discussed in the text).
Figure 2. Probability of disease with increased augmented methylprednisolone: cumulative probability of symptomatic disease according to viral load and methylprednisolone usage (Cope et al., ). Methylprednisolone usage: no drug given, purple line; one course, orange line; two courses, green line; three courses, red line and four courses, blue line. One course consists of 1 g a day for 3 days.


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Further Reading

Griffiths PD. The Stealth Virus.‐Virus‐Prof‐Paul‐Griffiths/dp/1477566791/ref=pd_sim_b_1?ie=UTF8&refRID=1G62W6AHH51S2V0JF23X.

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Griffiths, Paul D, and Lumley, Sheila(Jan 2015) Cytomegalovirus Infections in Humans. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002227.pub3]