title: Cytomegalovirus reactivation enhances the virulence of Staphylococcus aureus pneumonia in a mouse model.
abstract: OBJECTIVE
  Cytomegalovirus (CMV) reactivation in intensive care unit patients may increase mortality and favour bacterial pneumonia. We developed a murine model to compare the severity of staphylococcal pneumonia after CMV reactivation and in CMV-negative mice.
  
  
  METHODS
  Balb/c mice were primo-infected with murine cytomegalovirus (MCMV n=90) or received saline (control n=90). After latency, all mice underwent caecal ligation and puncture to trigger MCMV reactivation in MCMV primary-infected mice. Surviving animals received an intra-nasal inoculation with methicillin-susceptible Staphylococcus aureus (MSSA) to induce pneumonia. Mortality, lung bacterial count, histology and interferon-alpha and gamma serum levels were compared in MCMV reactivated and control mice 2, 5 and 15 days after pneumonia.
  
  
  RESULTS
  After MSSA pneumonia, MCMV mice showed a trend towards a higher mortality (9.4% versus 0%; p 0.09) and a higher weight loss (2.2 (0.6-4.1 g) versus 0.7 (-0.3 to 1.3 g); p 0.005). The lung bacterial count was higher in MCMV mice 2 days (5×103(103to 3×105) versus 102(0 to 4×102) CFU/lung; p 0.007) and 5 days (2.5×104(1.6×104to 6.5×105) versus 15 (10-40) CFU/lung; p 0.005) after MSSA pneumonia. 8/40 (20%) MCMV mice developed lung abscesses compared to 0% in control (p 0.011). Interferon-alpha serum levels 2 days after staphylococcal pneumonia were higher in MCMV mice.
  
  
  CONCLUSIONS
  MCMV reactivation decreased lung bacterial clearance and favoured the development of staphylococcal abscessing pneumonia. CMV reactivation may be responsible for a higher susceptibility to bacterial sepsis.
authors.affiliation: Aix-Marseille Univ, APHM, URMITE UMR CNRS 7278, Hôpital Nord, Réanimation des Détresses Respiratoires et Infections Sévères, Marseille, France; IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France. Electronic address: sami.hraiech@ap-hm.fr.
authors.forename: S
authors.initials: S
authors.lastname: Hraiech
authors.affiliation: IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France; Fédération d'Anesthésie-Réanimation-Urgences, Hôpital d'Instruction des Armées Sainte-Anne Toulon, France.
authors.forename: J
authors.initials: J
authors.lastname: Bordes
authors.affiliation: IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Mège
authors.affiliation: UMR "Emergence des Pathologies Virales" (EPV: Aix-Marseille Universite - IRD 190 - Inserm 1207 - EHESP), Marseille, France; Institut hospitalo-universitaire Méditerranée infection, APHM Public Hospitals of Marseille, Marseille, France.
authors.forename: X
authors.initials: X
authors.lastname: de Lamballerie
authors.affiliation: UMR "Emergence des Pathologies Virales" (EPV: Aix-Marseille Universite - IRD 190 - Inserm 1207 - EHESP), Marseille, France; Institut hospitalo-universitaire Méditerranée infection, APHM Public Hospitals of Marseille, Marseille, France.
authors.forename: R
authors.initials: R
authors.lastname: Charrel
authors.affiliation: IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Bechah
authors.affiliation: UMR "Emergence des Pathologies Virales" (EPV: Aix-Marseille Universite - IRD 190 - Inserm 1207 - EHESP), Marseille, France; Institut hospitalo-universitaire Méditerranée infection, APHM Public Hospitals of Marseille, Marseille, France.
authors.forename: B
authors.initials: B
authors.lastname: Pastorino
authors.affiliation: Aix-Marseille Univ, APHM, URMITE UMR CNRS 7278, Hôpital Nord, Réanimation des Détresses Respiratoires et Infections Sévères, Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Guervilly
authors.affiliation: Aix-Marseille Univ, APHM, URMITE UMR CNRS 7278, Hôpital Nord, Réanimation des Détresses Respiratoires et Infections Sévères, Marseille, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Forel
authors.affiliation: Aix-Marseille Univ, APHM, URMITE UMR CNRS 7278, Hôpital Nord, Réanimation des Détresses Respiratoires et Infections Sévères, Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: Adda
authors.affiliation: IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Rolain
authors.affiliation: IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France.
authors.forename: H
authors.initials: H
authors.lastname: Lepidi
authors.affiliation: IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France.
authors.forename: D
authors.initials: D
authors.lastname: Raoult
authors.affiliation: Aix-Marseille Univ, APHM, URMITE UMR CNRS 7278, Hôpital Nord, Réanimation des Détresses Respiratoires et Infections Sévères, Marseille, France.
authors.forename: S
authors.initials: S
authors.lastname: Lehingue
authors.affiliation: Aix-Marseille Univ, APHM, URMITE UMR CNRS 7278, Hôpital Nord, Réanimation des Détresses Respiratoires et Infections Sévères, Marseille, France; IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France.
authors.forename: L
authors.initials: L
authors.lastname: Papazian
mesh_terms: D000818:Animals; D060085:Coinfection; D003586:Cytomegalovirus Infections / Q000150:complications*; D051379:Mice; D018410:Pneumonia, Bacterial / Q000150:complications / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D014774:Virulence; D014775:Virus Activation
keywords: Cytomegalovirus reactivation; Intensive care unit; Lung abscesses; Murine model; Pneumonia; Staphylococcus aureus