nach oben

Medical Microbiology and Immunology

Erschienen in:

01.06.2015 | Review

Sepsis and cytomegalovirus: foes or conspirators?

verfasst von: Sara Mansfield, Marion Grießl, Michael Gutknecht, Charles H. Cook

Erschienen in: Medical Microbiology and Immunology | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

Cytomegalovirus (CMV) reactivation in non-immune-suppressed critically ill patients is an area of increasing interest. CMV has long been appreciated as a pathogen in immunocompromised hosts. CMV reactivates in approximately one-third of latently infected non-immune-suppressed hosts during critical illness; however, its role as a pathogen in these patients remains unclear. CMV reactivation has been linked to bacterial sepsis and likely results from inflammation, transient immune compromise, and viral epigenetic changes. While CMV may improve immune response to some bacterial infections, other data suggest that CMV induces exaggerated responses to severe infections that may be harmful to latently infected hosts. These results also suggest that previous infection history may explain significant differences seen between human septic responses and murine models of sepsis. While critically ill human hosts clearly have worse outcomes associated with CMV reactivation, determining causality remains an area of investigation, with randomized control trials currently being performed. Here we review the current literature and highlight areas for future investigation.

Smith MG (1954) Propagation of salivary gland virus of the mouse in tissue cultures. Proc Soc Exp Biol Med 86(3):435–440CrossRefPubMed

Smith MG (1956) Propagation in tissue cultures of a cytopathogenic virus from human salivary gland virus (SGV) disease. Proc Soc Exp Biol Med 92(2):424–430CrossRefPubMed

Guidry CA, Mansfield SA, Sawyer RG, Cook CH (2014) Resistant pathogens, fungi, and viruses. Surg Clin North Am 94(6):1195–1218. doi:10.1016/j.suc.2014.08.010 CrossRefPubMed

Cook CH, Trgovcich J (2011) Cytomegalovirus reactivation in critically ill immunocompetent hosts: a decade of progress and remaining challenges. Antivir Res 90(3):151–159. doi:10.1016/j.antiviral.2011.03.179 CrossRefPubMedCentralPubMed

Bordes J, Maslin J, Prunet B, d’Aranda E, Lacroix G, Goutorbe P, Dantzer E, Meaudre E (2011) Cytomegalovirus infection in severe burn patients monitoring by real-time polymerase chain reaction: a prospective study. Burns 37(3):434–439. doi:10.1016/j.burns.2010.11.006 CrossRefPubMed

Heininger A, Haeberle H, Fischer I, Beck R, Riessen R, Rohde F, Meisner C, Jahn G, Koenigsrainer A, Unertl K, Hamprecht K (2011) Cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis. Crit Care 15(2):R77. doi:10.1186/cc10069 CrossRefPubMedCentralPubMed

Heininger A, Jahn G, Engel C, Notheisen T, Unertl K, Hamprecht K (2001) Human cytomegalovirus infections in nonimmunosuppressed critically ill patients. Crit Care Med 29(3):541–547CrossRefPubMed

Chilet M, Aguilar G, Benet I, Belda J, Tormo N, Carbonell JA, Clari MA, Costa E, Navarro D (2010) Virological and immunological features of active cytomegalovirus infection in nonimmunosuppressed patients in a surgical and trauma intensive care unit. J Med Virol 82(8):1384–1391. doi:10.1002/jmv.21825 CrossRefPubMed

Ziemann M, Sedemund-Adib B, Reiland P, Schmucker P, Hennig H (2008) Increased mortality in long-term intensive care patients with active cytomegalovirus infection. Crit Care Med 36(12):3145–3150CrossRefPubMed

10.

Limaye AP, Kirby KA, Rubenfeld GD, Leisenring WM, Bulger EM, Neff MJ, Gibran NS, Huang M-L, Santo Hayes TK, Corey L, Boeckh M (2008) Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA 300(4):413–422. doi:10.1001/jama.300.4.413 CrossRefPubMedCentralPubMed

11.

von Muller L, Klemm A, Weiss M, Schneider M, Suger-Wiedeck H, Durmus N, Hampl W, Mertens T (2006) Active cytomegalovirus infection in patients with septic shock. Emerg Infect Dis 12(10):1517–1522CrossRef

12.

Kutza AS, Muhl E, Hackstein H, Kirchner H, Bein G (1998) High incidence of active cytomegalovirus infection among septic patients. Clin Infect Dis 26(5):1076–1082CrossRefPubMed

13.

Papazian L, Fraisse A, Garbe L, Zandotti C, Thomas P, Saux P, Pierrin G, Gouin F (1996) Cytomegalovirus. An unexpected cause of ventilator-associated pneumonia. Anesthesiology 84(2):280–287CrossRefPubMed

14.

Domart Y, Trouillet JL, Fagon JY, Chastre J, Brun-Vezinet F, Gibert C (1990) Incidence and morbidity of cytomegaloviral infection in patients with mediastinitis following cardiac surgery [see comments]. Chest 97(1):18–22CrossRefPubMed

15.

Walton AH, Muenzer JT, Rasche D, Boomer JS, Sato B, Brownstein BH, Pachot A, Brooks TL, Deych E, Shannon WD, Green JM, Storch GA, Hotchkiss RS (2014) Reactivation of multiple viruses in patients with sepsis. PLoS ONE 9(6):e98819. doi:10.1371/journal.pone.0098819 CrossRefPubMedCentralPubMed

16.

Coisel Y, Bousbia S, Forel J-M, Hraiech S, Lascola B, Roch A, Zandotti C, Million M, Jaber S, Raoult D, Papazian L (2012) Cytomegalovirus and herpes simplex virus effect on the prognosis of mechanically ventilated patients suspected to have ventilator-associated pneumonia. PLoS ONE 7(12):e51340. doi:10.1371/journal.pone.0051340 CrossRefPubMedCentralPubMed

17.

Smith CA, Conroy LT, Pollock M, Ruddy J, Binning A, McCruden EA (2010) Detection of herpes viruses in respiratory secretions of patients undergoing artificial ventilation. J Med Virol 82(8):1406–1409. doi:10.1002/jmv.21794 CrossRefPubMed

18.

Jaber S, Chanques G, Borry J, Souche B, Verdier R, Perrigault P-F, Eledjam J-J (2005) Cytomegalovirus infection in critically ill patients: associated factors and consequences. Chest 127(1):233–241CrossRefPubMed

19.

Friedrichs I, Bingold T, Keppler OT, Pullmann B, Reinheimer C, Berger A (2013) Detection of herpesvirus EBV DNA in the lower respiratory tract of ICU patients: a marker of infection of the lower respiratory tract? Med Microbiol Immunol 202(6):431–436. doi:10.1007/s00430-013-0306-1 CrossRefPubMed

20.

Chiche L, Forel JM, Roch A, Guervilly C, Pauly V, Allardet-Servent J, Gainnier M, Zandotti C, Papazian L (2009) Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients. Crit Care Med 37(6):1850–1857CrossRefPubMed

21.

Cook CH, Martin LC, Yenchar JK, Lahm MC, McGuinness B, Davies EA, Ferguson RM (2003) Occult herpes family viral infections are endemic in critically ill surgical patients. Crit Care Med 31(7):1923–1929CrossRefPubMed

22.

Cook CH, Yenchar JK, Kraner TO, Davies EA, Ferguson RM (1998) Occult herpes family viruses may increase mortality in critically ill surgical patients. Am J Surg 176(4):357–360CrossRefPubMed

23.

Desachy A, Ranger-Rogez S, Francois B, Venot C, Traccard I, Gastinne H, Denis F, Vignon P (2001) Reactivation of human herpesvirus type 6 in multiple organ failure syndrome. Clin Infect Dis 32(2):197–203CrossRefPubMed

24.

Razonable RR, Fanning C, Brown RA, Espy MJ, Rivero A, Wilson J, Kremers W, Smith TF, Paya CV (2002) Selective reactivation of human herpesvirus 6 variant a occurs in critically ill immunocompetent hosts.[see comment]. J Infect Dis 185(1):110–113CrossRefPubMed

25.

Stephan F, Meharzi D, Ricci S, Fajac A, Clergue F, Bernaudin JF (1996) Evaluation by polymerase chain reaction of cytomegalovirus reactivation in intensive care patients under mechanical ventilation. Intensiv Care Med 22(11):1244–1249CrossRef

26.

Vogel T, Vadonis R, Kuehn J, Eing BR, Senninger N, Haier J (2008) Viral reactivation is not related to septic complications after major surgical resections. APMIS 116(4):292–301CrossRefPubMed

27.

Ishioka H, Sanui M, Tsutsumi Y, Yanase F, Shiotsuka J (2014) Low prevalence of active cytomegalovirus infection in a cardiovascular intensive care unit. J Intensiv Care 2(1):12. doi:10.1186/2052-0492-2-12 CrossRef

28.

Docke WD, Prosch S, Fietze E, Kimel V, Zuckermann H, Klug C, Syrbe U, Kruger DH, von Baehr R, Volk HD (1994) Cytomegalovirus reactivation and tumour necrosis factor. Lancet 343(8892):268–269CrossRefPubMed

29.

Stein J, Volk HD, Liebenthal C, Kruger DH, Prosch S (1993) Tumour necrosis factor alpha stimulates the activity of the human cytomegalovirus major immediate early enhancer/promoter in immature monocytic cells. J Gen Virol 74(11):2333–2338CrossRefPubMed

30.

Prosch S, Staak K, Stein J, Liebenthal C, Stamminger T, Volk HD, Kruger DH (1995) Stimulation of the human cytomegalovirus IE enhancer/promoter in HL-60 Cells by TNF alpha is mediated via induction of NF-kappaB. Virology 208(1):197–206CrossRefPubMed

31.

Cook C, Zhang X, McGuinness B, Lahm M, Sedmak D, Ferguson R (2002) Intra-abdominal bacterial infection reactivates latent pulmonary cytomegalovirus in immunocompetent mice. J Infect Dis 185:1395–1400CrossRefPubMed

32.

Cook CH, Trgovcich J, Zimmerman PD, Zhang Y, Sedmak DD (2006) Lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1{beta} triggers reactivation of latent cytomegalovirus in immunocompetent mice. J Virol 80(18):9151–9158CrossRefPubMedCentralPubMed

33.

Seckert CK, Griessl M, Buttner JK, Freitag K, Lemmermann N, Hummel M, Liu XF, Abecassis M, Angulo A, Messerle M, Cook CH, Reddehase M (2013) Immune Surveillance of Cytomegalovirus Latency and Reactivation in Murine Models: Link to Memory Inflation. In: Reddehase MJ (ed) Cytomegaloviruses, vol 1., Caister Academic PressNorfolk, UK, pp 374–416

34.

Cook CH, Zhang Y, Sedmak DD, Martin LC, Jewell S, Ferguson RM (2006) Pulmonary cytomegalovirus reactivation causes pathology in immunocompetent mice. Crit Care Med 34(3):842–849PubMedCentralPubMed

35.

Barton ES, White DW, Cathelyn JS, Brett-McClellan KA, Engle M, Diamond MS, Miller VL, Virgin HW (2007) Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447(7142):326–329CrossRefPubMed

36.

Smith PD, Shimamura M, Musgrove LC, Dennis EA, Bimczok D, Novak L, Ballestas M, Fenton A, Dandekar S, Britt WJ, Smythies LE (2014) Cytomegalovirus enhances macrophage TLR expression and MyD88-mediated signal transduction to potentiate inducible inflammatory responses. J Immunol 193:5604–5612. doi:10.4049/jimmunol.1302608 CrossRefPubMed

37.

Tanaka K, Sawamura S, Satoh T, Kobayashi K, Noda S (2007) Role of the indigenous microbiota in maintaining the virus-specific CD8 memory T cells in the lung of mice infected with murine cytomegalovirus. J Immunol 178(8):5209–5216CrossRefPubMed

38.

Seckert CK, Griessl M, Buttner JK, Scheller S, Simon CO, Kropp KA, Renzaho A, Kuhnapfel B, Grzimek NK, Reddehase MJ (2012) Viral latency drives ‘memory inflation’: a unifying hypothesis linking two hallmarks of cytomegalovirus infection. Med Microbiol Immunol. doi:10.1007/s00430-012-0273-y PubMed

39.

Kurz SK, Reddehase MJ (1999) Patchwork pattern of transcriptional reactivation in the lungs indicates sequential checkpoints in the transition from murine cytomegalovirus latency to recurrence. J Virol 73(10):8612–8622PubMedCentralPubMed

40.

De Vlieger G, Meersseman W, Lagrou K, Wouters P, Wilmer A, Peetermans W, Van den Berghe G, Van Wijngaerden E (2012) Cytomegalovirus serostatus and outcome in nonimmunocompromised critically ill patients. Crit Care Med 40(1):36–42CrossRefPubMed

41.

Simanek AM, Dowd JB, Pawelec G, Melzer D, Dutta A, Aiello AE (2011) Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States. PLoS ONE 6(2):e16103. doi:10.1371/journal.pone.0016103 CrossRefPubMedCentralPubMed

42.

Strandberg TE, Pitkala KH, Tilvis RS (2009) Cytomegalovirus antibody level and mortality among community-dwelling older adults with stable cardiovascular disease. JAMA 301(4):380–382CrossRefPubMed

43.

Wang GC, Kao WHL, Murakami P, Xue Q-L, Chiou RB, Detrick B, McDyer JF, Semba RD, Casolaro V, Walston JD, Fried LP (2010) Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol 171(10):1144–1152. doi:10.1093/aje/kwq062 CrossRefPubMedCentralPubMed

44.

Miggins M, Hasan A, Hohmann S, Southwick F, Casella G, Schain D, Liu H, Bihorac A, Moldawer L, Efron P, Ang D (2011) The potential influence of common viral infections diagnosed during hospitalization among critically ill patients in the United States. PLoS ONE 6(4):e18890CrossRefPubMedCentralPubMed

45.

Sylwester AW, Mitchell BL, Edgar JB, Taormina C, Pelte C, Ruchti F, Sleath PR, Grabstein KH, Hosken NA, Kern F, Nelson JA, Picker LJ (2005) Broadly targeted human cytomegalovirus-specific CD4⁺ and CD8⁺ T cells dominate the memory compartments of exposed subjects. J Exp Med 202(5):673–685. doi:10.1084/jem.20050882 CrossRefPubMedCentralPubMed

46.

Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, Lopez CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA. doi:10.1073/pnas.1222878110

47.

Welsh RM, Selin LK (2002) No one is naive: the significance of heterologous T-cell immunity. Nat Rev Immunol 2(6):417–426PubMed

48.

Barton ES, White DW, Virgin HW (2009) Herpesvirus latency and symbiotic protection from bacterial infection. Viral Immunol 22(1):3–4. doi:10.1089/vim.2008.0100 CrossRefPubMedCentralPubMed

49.

Kalil AC, Florescu DF (2009) Prevalence and mortality associated with cytomegalovirus infections in non-immunosuppressed ICU patients. Crit Care Med 37(8):2350–2358CrossRefPubMed

50.

Wohl DA, Zeng D, Stewart P, Glomb N, Alcorn T, Jones S, Handy J, Fiscus S, Weinberg A, Gowda D, van der Horst C (2005) Cytomegalovirus viremia, mortality, and end-organ disease among patients with AIDS receiving potent antiretroviral therapies. JAIDS J Acquir Immune Defic Syndr 38(5):538–544CrossRef

51.

Hotchkiss RS, Coopersmith CM, McDunn JE, Ferguson TA (2009) The sepsis seesaw: tilting toward immunosuppression. Nat Med 15(5):496–497CrossRefPubMedCentralPubMed

52.

Campbell J, Trgovcich J, Kincaid M, Zimmerman PD, Klenerman P, Sims S, Cook CH (2012) Transient CD8-memory contraction: a potential contributor to latent cytomegalovirus reactivation. J Leukoc Biol 92(5):933–937. doi:10.1189/jlb.1211635 CrossRefPubMedCentralPubMed

53.

von Muller L, Mertens T (2008) Human cytomegalovirus infection and antiviral immunity in septic patients without canonical immunosuppression. Med Microbiol Immunol 197(2):75–82CrossRef

54.

Seckert CK, Renzaho A, Tervo H-M, Krause C, Deegen P, Kuhnapfel B, Reddehase MJ, Grzimek NKA (2009) Liver sinusoidal endothelial cells are a site of murine cytomegalovirus latency and reactivation. J Virol 83(17):8869–8884. doi:10.1128/jvi.00870-09 CrossRefPubMedCentralPubMed

55.

Balthesen M, Messerle M, Reddehase MJ (1993) Lungs are a major organ site of cytomegalovirus latency and recurrence. J Virol 67(9):5360–5366PubMedCentralPubMed

56.

Toorkey CB, Carrigan DR (1989) Immunohistochemical detection of an immediate early antigen of human cytomegalovirus in normal tissues. J Infect Dis 160(5):741–751CrossRefPubMed

57.

Cook CH (2007) Cytomegalovirus reactivation in “immunocompetent” patients: a call for scientific prophylaxis. J Infect Dis 196(9):1273–1275CrossRefPubMed

58.

Kalil AC, Levitsky J, Lyden E, Stoner J, Freifeld AG (2005) Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med 143(12):870–880CrossRefPubMed

59.

Forster MR, Trgovcich J, Zimmerman P, Chang A, Miller C, Klenerman P, Cook CH (2010) Antiviral prevention of sepsis induced cytomegalovirus reactivation in immunocompetent mice. Antivir Res 85(3):496–503. doi:10.1016/j.antiviral.2009.12.004 CrossRefPubMedCentralPubMed

60.

Traen S, Bochanen N, Ieven M, Schepens T, Bruynseels P, Verbrugghe W, Jorens PG (2014) Is acyclovir effective among critically ill patients with herpes simplex in the respiratory tract? J Clin Virol 60(3):215–221. doi:10.1016/j.jcv.2014.04.010 CrossRefPubMed

Titel: Sepsis and cytomegalovirus: foes or conspirators?
verfasst von: Sara Mansfield
Marion Grießl
Michael Gutknecht
Charles H. Cook
Publikationsdatum: 01.06.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Medical Microbiology and Immunology / Ausgabe 3/2015
Print ISSN: 0300-8584
Elektronische ISSN: 1432-1831
DOI: https://doi.org/10.1007/s00430-015-0407-0

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypotonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Sepsis and cytomegalovirus: foes or conspirators?

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2015

Principles for studying in vivo attenuation of virus mutants: defining the role of the cytomegalovirus gH/gL/gO complex as a paradigm

The proteome of human cytomegalovirus virions and dense bodies is conserved across different strains

Margaret Gladys Smith, mother of cytomegalovirus: 60th anniversary of cytomegalovirus isolation

How understanding immunology contributes to managing CMV disease in immunosuppressed patients: now and in future

Mast cells: innate attractors recruiting protective CD8 T cells to sites of cytomegalovirus infection

Manipulation of apoptosis and necroptosis signaling by herpesviruses

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin