Cytomegalovirus infection pathophysiology: Difference between revisions

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{{CMG}}; {{AE}}{{QS}}
{{CMG}}; {{AE}}{{QS}}
==Overview==
==Overview==
Transmission of [[CMV]] occurs from person to person and primary [[CMV infection]] causes activation of the [[immune system]] and resulting in a [[mononucleosis]] like presentation with [[hepatitis]] in [[immunocompromised]] individuals and few [[immunocompetent]] individuals. 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.
==Pathophysiology==
==Pathophysiology==
===Transmission===
===Transmission===
*Transmission of CMV occurs from person to person.
*Transmission of [[CMV]] occurs from person to person.<ref name="pmid25205255">{{cite journal| author=Griffiths P, Baraniak I, Reeves M| title=The pathogenesis of human cytomegalovirus. | journal=J Pathol | year= 2015 | volume= 235 | issue= 2 | pages= 288-97 | pmid=25205255 | doi=10.1002/path.4437 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25205255  }} </ref>
* [[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.<ref>{{cite journal | author=Staras SAS, Dollard SC, Radford KW, ''et al.'' | title=Seroprevalence of cytomegalovirus infection in the United States, 1988&ndash;1994 | year=2006 | journal=Clin Infect Dis | volume=43 | pages=1143&ndash;51 | pmid = 17029132}}</ref>  
*Infection requires close, intimate contact with a person excreting the virus in their [[saliva]], [[urine]], [[blood]], [[tears]], and [[semen]].  
*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.  
*The shedding of [[virus]] may take place intermittently, without any detectable signs, and without causing symptoms.  
*CMV can be [[Sexually transmitted disease|sexually transmitted]] and can also be transmitted via [[Breastfeeding|breast milk]], transplanted organs, and rarely from [[blood transfusion]]s.
*CMV can be [[Sexually transmitted disease|sexually transmitted]] and can also be transmitted via [[Breastfeeding|breast milk]], transplanted organs, and rarely from [[blood transfusion]]s.<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | pages = pp. 556; 566–9 | publisher = McGraw Hill | year = 2004 | isbn = 0838585299 }}</ref>
*Although CMV is not highly contagious, it has been shown to spread in households and among young children in day care centers.<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | pages = pp. 556; 566–9 | publisher = McGraw Hill | year = 2004 | isbn = 0838585299 }}</ref>
 
===Pathogenesis===
===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.<ref>{{cite journal | author=Staras SAS, Dollard SC, Radford KW, ''et al.'' | title=Seroprevalence of cytomegalovirus infection in the United States, 1988&ndash;1994 | year=2006 | journal=Clin Infect Dis | volume=43 | pages=1143&ndash;51 | pmid = 17029132}}</ref><ref name="pmid25097085">{{cite journal| author=Goodman AL, Murray CD, Watkins J, Griffiths PD, Webster DP| title=CMV in the gut: a critical review of CMV detection in the immunocompetent host with colitis. | journal=Eur J Clin Microbiol Infect Dis | year= 2015 | volume= 34 | issue= 1 | pages= 13-8 | pmid=25097085 | doi=10.1007/s10096-014-2212-x | pmc=4281362 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25097085  }} </ref><ref name="pmid18371229">{{cite journal| author=Rafailidis PI, Mourtzoukou EG, Varbobitis IC, Falagas ME| title=Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. | journal=Virol J | year= 2008 | volume= 5 | issue=  | pages= 47 | pmid=18371229 | doi=10.1186/1743-422X-5-47 | pmc=2289809 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18371229  }} </ref><ref name="pmid27460032">{{cite journal| author=Khan TV, Toms C| title=Cytomegalovirus Colitis and Subsequent New Diagnosis of Inflammatory Bowel Disease in an Immunocompetent Host: A Case Study and Literature Review. | journal=Am J Case Rep | year= 2016 | volume= 17 | issue=  | pages= 538-43 | pmid=27460032 | doi= | pmc=4968430 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27460032  }} </ref><ref name="pmid18194509">{{cite journal| author=Einbinder Y, Wolf DG, Pappo O, Migdal A, Tsvang E, Ackerman Z| title=The clinical spectrum of cytomegalovirus colitis in adults. | journal=Aliment Pharmacol Ther | year= 2008 | volume= 27 | issue= 7 | pages= 578-87 | pmid=18194509 | doi=10.1111/j.1365-2036.2008.03595.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18194509  }} </ref>
*Primary [[CMV infection]] causes activation of the [[immune system]] and results in a [[mononucleosis]] like presentation and its complications in [[immunocompromised]] individuals and few [[immunocompetent]] individuals.<ref>{{cite journal | author=Staras SAS, Dollard SC, Radford KW, ''et al.'' | title=Seroprevalence of cytomegalovirus infection in the United States, 1988&ndash;1994 | year=2006 | journal=Clin Infect Dis | volume=43 | pages=1143&ndash;51 | pmid = 17029132}}</ref><ref name="pmid25097085">{{cite journal| author=Goodman AL, Murray CD, Watkins J, Griffiths PD, Webster DP| title=CMV in the gut: a critical review of CMV detection in the immunocompetent host with colitis. | journal=Eur J Clin Microbiol Infect Dis | year= 2015 | volume= 34 | issue= 1 | pages= 13-8 | pmid=25097085 | doi=10.1007/s10096-014-2212-x | pmc=4281362 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25097085  }} </ref><ref name="pmid18371229">{{cite journal| author=Rafailidis PI, Mourtzoukou EG, Varbobitis IC, Falagas ME| title=Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. | journal=Virol J | year= 2008 | volume= 5 | issue=  | pages= 47 | pmid=18371229 | doi=10.1186/1743-422X-5-47 | pmc=2289809 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18371229  }} </ref><ref name="pmid27460032">{{cite journal| author=Khan TV, Toms C| title=Cytomegalovirus Colitis and Subsequent New Diagnosis of Inflammatory Bowel Disease in an Immunocompetent Host: A Case Study and Literature Review. | journal=Am J Case Rep | year= 2016 | volume= 17 | issue=  | pages= 538-43 | pmid=27460032 | doi= | pmc=4968430 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27460032  }} </ref><ref name="pmid18194509">{{cite journal| author=Einbinder Y, Wolf DG, Pappo O, Migdal A, Tsvang E, Ackerman Z| title=The clinical spectrum of cytomegalovirus colitis in adults. | journal=Aliment Pharmacol Ther | year= 2008 | volume= 27 | issue= 7 | pages= 578-87 | pmid=18194509 | doi=10.1111/j.1365-2036.2008.03595.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18194509  }} </ref>
*In majority of immunocompetent people, primary CMV infection is sub clinical and asymptomatic.
*In majority of [[immunocompetent]] people, primary [[Cytomegalovirus infection|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.
*Following primary infection the [[virus]] persists in a latent form in the host tissues invading the [[immune system]].<ref name="pmid25772624">{{cite journal| author=Poole E, Sinclair J| title=Sleepless latency of human cytomegalovirus. | journal=Med Microbiol Immunol | year= 2015 | volume= 204 | issue= 3 | pages= 421-9 | pmid=25772624 | doi=10.1007/s00430-015-0401-6 | pmc=4439429 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25772624  }} </ref>
*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.
*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.
*[[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.
*In patients with [[T cell|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.
*Reactivation of the [[virus]] results in the release of [[cytokines]] such as  [[TNF-α]] and [[Interferon gamma|IFN-γ]] resulting in [[inflammation]].


===Genetics===
===Genetics===
There are no genetic factors predisposing individuals for cytomegalovirus infection.
*Patients with [[polymorphisms]] in the [[genes]] coding for mannose binding [[lectin]] and ficolin-2 are at a higher risk of developing [[CMV infection]].<ref name="pmid27108521">{{cite journal| author=Klenerman P, Oxenius A| title=T cell responses to cytomegalovirus. | journal=Nat Rev Immunol | year= 2016 | volume= 16 | issue= 6 | pages= 367-77 | pmid=27108521 | doi=10.1038/nri.2016.38 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27108521  }} </ref>


===Associated Conditions===
===Associated Conditions===
*Symptomatic cytomegalovirus is associated with HIV infection in majority of patients.
*Symptomatic [[cytomegalovirus]] is associated with [[HIV AIDS|HIV infection]] in majority of patients.<ref name="pmid27714898">{{cite journal| author=Grønborg HL, Jespersen S, Hønge BL, Jensen-Fangel S, Wejse C| title=Review of cytomegalovirus coinfection in HIV-infected individuals in Africa. | journal=Rev Med Virol | year= 2017 | volume= 27 | issue= 1 | pages=  | pmid=27714898 | doi=10.1002/rmv.1907 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27714898  }} </ref><ref name="pmid27625433">{{cite journal| author=Gianella S, Letendre S| title=Cytomegalovirus and HIV: A Dangerous Pas de Deux. | journal=J Infect Dis | year= 2016 | volume= 214 Suppl 2 | issue=  | pages= S67-74 | pmid=27625433 | doi=10.1093/infdis/jiw217 | pmc=5021239 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27625433  }} </ref>


===Microscopic Pathology===
===Microscopic Pathology===
Microscopically, CMV infection can be demonstrated by the presence of [[intranuclear]] [[inclusion]] bodies. These inclusion bodies stain dark pink on an [[H&E stain]], and are also called "Owl's Eye" inclusion bodies.
*[[CMV infection]] demonstrates the presence of [[intranuclear]] [[inclusion]] bodies. These [[inclusion bodies]] stain dark pink on an [[H&E stain]], and are also called "Owl's Eye" [[inclusion bodies]].


==References==
==References==
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Latest revision as of 21:13, 29 July 2020

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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

Transmission of CMV occurs from person to person and primary CMV infection causes activation of the immune system and resulting in a mononucleosis like presentation with hepatitis in immunocompromised individuals and few immunocompetent individuals. 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.

Pathophysiology

Transmission

Pathogenesis

Genetics

Associated Conditions

Microscopic Pathology

References

  1. Griffiths P, Baraniak I, Reeves M (2015). "The pathogenesis of human cytomegalovirus". J Pathol. 235 (2): 288–97. doi:10.1002/path.4437. PMID 25205255.
  2. Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed. ed.). McGraw Hill. pp. pp. 556, 566–9. ISBN 0838585299.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Poole E, Sinclair J (2015). "Sleepless latency of human cytomegalovirus". Med Microbiol Immunol. 204 (3): 421–9. doi:10.1007/s00430-015-0401-6. PMC 4439429. PMID 25772624.
  9. Klenerman P, Oxenius A (2016). "T cell responses to cytomegalovirus". Nat Rev Immunol. 16 (6): 367–77. doi:10.1038/nri.2016.38. PMID 27108521.
  10. Grønborg HL, Jespersen S, Hønge BL, Jensen-Fangel S, Wejse C (2017). "Review of cytomegalovirus coinfection in HIV-infected individuals in Africa". Rev Med Virol. 27 (1). doi:10.1002/rmv.1907. PMID 27714898.
  11. Gianella S, Letendre S (2016). "Cytomegalovirus and HIV: A Dangerous Pas de Deux". J Infect Dis. 214 Suppl 2: S67–74. doi:10.1093/infdis/jiw217. PMC 5021239. PMID 27625433.

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