Detection of latent human cytomegalovirus in organ tissue and the correlation with serological status

Abstract

The presence of human cytomegalovirus (HCMV) genome in spleen tissue was studied by using DNA hybridization techniques in seropositive and seronegative organ donors without clinical or laboratory confirmed HCMV infection. The serum samples of these patients were screened by latex agglutination test (LA) and enzyme linked immuno sorbent assay (ELISA) for the presence of HCMV antibodies, and confirmed by immunoblotting technique (IB ). For the detection of HCMV sequences in spleen tissue dot blot DNA hybridization (DBH) using probes derived from immediate-early and late regions (ES and BH fragment respectively) of the HCMV genome were used. Samples positive in DBH were further tested by in situ DNA hybridization (ISH) using the ES probe. The number of spleen tissue specimens positive for HCMV nucleic acids indicated that HCMV may be present in human beings, even without serological evidence.Human cytomegalovirus (HCMV), a member of the herpesvirus family, is an ubiquitous human viral pathogen. Infection with HCMV is usually asymptomatic in the immunocompetent host, but can result in a dramatic disease in immunosuppressed patients [15]. After primary infection the virus persists in the host as a chronic or latent infection, which can periodically reactivate to an active infection. HCMV is known to be transmitted through blood transfusions [1,24] and transplanted organs [10,33] which can result in a severe HCMV disease, especially in immunosuppressed and seronegative patients [3,22]. Several studies indicate that in HCMV seropositive healthy individuals latent infection can be demonstrated by the presence of HCMV antigens. This is done by immunohistochemical techniques or by the detecting the presence of Offprint requests to: Y. J. Kraat,

The role of cytomegalovirus in prostate cancer incidence and mortality

“…Many men who were CMV seronegative still had CMV infected prostates. This is not surprising, as it is well established that CMV serostatus substantially underestimates the proportion of individuals who are infected by CMV [15][16][17][18][19][20][21][22] . Thus, we are not exclusively comparing groups of individuals who are CMV infected or not, but who are infected to varying degrees.…”

“…In CMV seropositive post-mortem donors (24/41, 59%), the proportion of the prostate epithelial cells that was infected by CMV ranged from 2% to 100% with a mean of 58%, as assessed by the detection of the CMV protein pp71 by IHC (n=24, Figure 1A). It is well established that CMV infected individuals often are seronegative [15][16][17][18][19][20][21][22][23][24][25][26] , and prostates from the 17 CMV seronegative post-mortem donors were all CMV IHC positive, but epithelial abundance of CMV was significantly lower than in CMV seropositive post-mortem donors with a mean of 28% (p<0.0001, Figure 1A).…”

“…CMV seropositivity likely underestimates the infected proportion of the population because CMV DNA is often detected along with low abundance of CMV responsive B-and/or T-cells in seronegative individuals [15][16][17][18][19][20][21][22][23][24][25][26] . These findings suggest that individuals are infected but have failed to mount a detectable antibody response.…”

Human cytomegalovirus strain diversity and dynamics reveal the donor lung as a major contributor after transplantation

“…Although several previous studies found that reinfection with donor-derived strains are more common than reactivation of recipient virus (Grundy et al, 1988)(Chou, 1986)(Sunwen & Norman, 1988), others have argued that infections post-transplantation are approximately equally donor- and recipient-derived (Manuel, Pang, et al, 2009). Reports on the detection of HCMV in tissues of non-immunocompromised individuals (Schonian et al, 1993)(Kytö et al, 2005)(Kraat et al, 1992)(Hendrix et al, 1997)(Meyer-König et al, 1998) further underline the potential of HCMV transmission with the allograft, yet the extent of transmission remained controversial. In the present study, we could demonstrate HCMV-DNA positivity in 5/10 pre-transplant lungs of HCMV-seropositive donors, with up to three HCMV genotypes present in small HCMV-DNA positive tissue sections of a single donor lung.…”

Cytomegalovirus promotes proliferation and survival of prostate cancer cells and constitutes a therapeutic target

“…Human cytomegalovirus (CMV) is a herpes virus, which the majority of humans are chronically infected by, indicated by 83% having antibodies against the virus 6 . This is likely a substantial underestimation of the proportion of the population that is infected, as it is very common to detect CMV DNA in seronegative individuals [7][8][9][10][11][12][13][14] , indicating that they are infected but lack a detectable antibody response. CMV seropositivity is associated with increased general cancer mortality in men 15 , but not associated with prostate cancer incidence 16,17 .…”