Cytomegalovirus infection pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qasim Salau, M.B.B.S., FMCPaed [2]
Overview
Pathophysiology
Transmission
- Transmission of CMV occurs from person to person.
- Seroprevalence is age-dependent: 58.9% of individuals aged 6 and over are infected with CMV while 90.8% of individuals aged 80 and over are positive for CMV.[1]
- Infection requires close, intimate contact with a person excreting the virus in their saliva, urine, blood, tears, and semen.
- The shedding of virus may take place intermittently, without any detectable signs, and without causing symptoms.
- CMV can be sexually transmitted and can also be transmitted via breast milk, transplanted organs, and rarely from blood transfusions.
- Although CMV is not highly contagious, it has been shown to spread in households and among young children in day care centers.[2]
Pathogenesis
- Primary CMV infection causes activation of the immune system and results in a mononucleosis like presentation with hepatitis in immunocompromised individuals and few immunocompetent individuals.[3][4][5][6][7]
- In majority of immunocompetent people, primary CMV infection is sub clinical and asymptomatic.
- Following primary infection the virus persists in a latent form in the host tissues invading the immune system.
- Reactivation can occur in response to inflammatory stimuli, physiologic stress and immunosuppression releasing new virions that can infect new cells causing cmv end organ infection.
- T-cells play a role in controlling the replication of the virus.
- In patients with T-cell deficiency the viral replication is uncontrolled and results in excessive shedding of the virus.
- Reactivation of the virus results in the release of cytokines such as TNF-α and IFN-γ resulting in inflammation.
Genetics
As a result of efforts to create an attenuated virus vaccine, there currently exist two general classes of CMV.
- Clinical isolates comprise those viruses obtained from patients and represent the wild type viral genome.
- Laboratory strains have been cultured extensively in the lab setting and typically contain numerous accumulated mutations. Most notably, the laboratory strain AD169 appears to lack a 15kb region of the 200kb genome that is present in clinical isolates. This region contains 19 open reading frames whose functions have yet to be elucidated. AD169 is also unique in that it is unable to enter latency and nearly always assumes lytic growth upon infection.
Associated Conditions
Symptomatic cytomegalovirus is associated with HIV infection in majority of patients.
Microscopic Pathology
Microscopically, CMV infection can be demonstrated by intranuclear inclusion bodies. These inclusion bodies stain dark pink on an H&E stain, and are also called "Owl's Eye" inclusion bodies.
References
- ↑ Staras SAS, Dollard SC, Radford KW; et al. (2006). "Seroprevalence of cytomegalovirus infection in the United States, 1988–1994". Clin Infect Dis. 43: 1143&ndash, 51. PMID 17029132.
- ↑ Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed. ed.). McGraw Hill. pp. pp. 556, 566–9. ISBN 0838585299.
- ↑ Staras SAS, Dollard SC, Radford KW; et al. (2006). "Seroprevalence of cytomegalovirus infection in the United States, 1988–1994". Clin Infect Dis. 43: 1143&ndash, 51. PMID 17029132.
- ↑ Goodman AL, Murray CD, Watkins J, Griffiths PD, Webster DP (2015). "CMV in the gut: a critical review of CMV detection in the immunocompetent host with colitis". Eur J Clin Microbiol Infect Dis. 34 (1): 13–8. doi:10.1007/s10096-014-2212-x. PMC 4281362. PMID 25097085.
- ↑ Rafailidis PI, Mourtzoukou EG, Varbobitis IC, Falagas ME (2008). "Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review". Virol J. 5: 47. doi:10.1186/1743-422X-5-47. PMC 2289809. PMID 18371229.
- ↑ Khan TV, Toms C (2016). "Cytomegalovirus Colitis and Subsequent New Diagnosis of Inflammatory Bowel Disease in an Immunocompetent Host: A Case Study and Literature Review". Am J Case Rep. 17: 538–43. PMC 4968430. PMID 27460032.
- ↑ Einbinder Y, Wolf DG, Pappo O, Migdal A, Tsvang E, Ackerman Z (2008). "The clinical spectrum of cytomegalovirus colitis in adults". Aliment Pharmacol Ther. 27 (7): 578–87. doi:10.1111/j.1365-2036.2008.03595.x. PMID 18194509.