Co‐infection of two β‐herpesviruses (CMV and HHV‐7) as an increased risk factor for ‘CMV disease’ in patients undergoing renal transplantation

Abstract

The ubiquity of human cytomegalovirus (CMV) and human herpesvirus-7 (HHV-7), as well as activation of these viruses during immunosuppression, allows the suggestion that both viruses could participate in the development of 'CMV disease' in patients after renal transplantation (RT). The aim of our research was to study the prevalence of latent CMV and HHV-7 infections in patients before RT, to determine interaction between these viruses in dual infection and possible association of their reactivation with the progression of 'CMV disease' after RT. Peripheral blood samples were collected from 49 patients before and up to 10-12 wk after RT. The methods used for diagnostics of viral infections were: serology, nested polymerase chain reaction (nPCR) analysis of peripheral blood leukocytes (PBL) and plasma, and virus isolation in cell cultures (morphological changes, nPCR analysis of cellular and cell-free samples, indirect immunofluorescence analysis). Before RT, CMV and HHV-7 DNAs were detected in PBL but not in the plasma samples, which indicates the presence of latent viral infection in patients. Latent dual (CMV + HHV-7) infection was prevalent (51.0%) in 49 patients, while CMV and HHV-7 infections alone were detected in 26.5 and 12.2% of patients, respectively. Risk of viral disease after RT, for recipients with latent dual infection before RT, was 12- and 2.2-fold higher in comparison with CMV and HHV-7 infections alone, respectively. Frequency of dual infection in 18 recipients with 'viral syndrome' or 'CMV disease' after RT was reliably higher (13/18, 81.3%) than CMV (1/18, 6.2%) (p < 0.025) and HHV-7 (2/18, 12.5%) (p < 0.025) infections alone. HHV-7 reactivation preceded CMV reactivation in 77.0% of the cases of dual infection in the recipients with viral disease and reactivation of both viruses preceded the development of viral disease. Severe 'CMV disease' developed in 2 out of 2 recipients with CMV primary infection and 'viral syndrome' in 1 recipient with CMV reinfection. The reactivation of CMV was detected in all recipients prior to onset of the disease. Correlation was shown between reactivation of latent HHV-7 infection and development of febrile syndrome in 2 out of 2 recipients with HHV-7 infection alone. Taking into account that dual infection is an increased risk factor for 'viral syndrome' and 'CMV disease' development, screening diagnostic should include testing for both viral infections in transplant donors as well as in recipients before and after RT.

Prevalence of blood-borne viral infections (cytomegalovirus, human herpesvirus-6, human herpesvirus-7, human herpesvirus-8, human T-cell lymphotropic virus-I/II, human retrovirus-5) among blood donors in Latvia

“…HHV-7 reactivation precedes reactivation of CMV, and this virus can act as a helper virus for CMV and HHV-6 reactivation [7,18]. Chapenko et al showed a correlation between reactivation of latent HHV-7 infection and development of febrile syndrome in two kidney transplant recipients with HHV-7 infection alone [7]. The above, as well as our observation of HHV-7 replication in 10.6% of individuals, of whom two also had latent CMV infection, suggest the importance of monitoring for herpesvirus infection among blood donors, especially regarding transfusion into immunocompromised recipients.…”

“…Recent studies demonstrated that concurrent dual β-herpesvirus infections were an increased risk factor for "viral syndrome" and "CMV disease" development in patients undergoing renal transplantation [7,18,26]. HHV-7 reactivation precedes reactivation of CMV, and this virus can act as a helper virus for CMV and HHV-6 reactivation [7,18]. Chapenko et al showed a correlation between reactivation of latent HHV-7 infection and development of febrile syndrome in two kidney transplant recipients with HHV-7 infection alone [7].…”

“…We showed that single, dual, or triple concurrent infection by CMV, HHV-6, and HHV-7 was detected in a high proportion of Latvian blood donors and that PBL were the target for this infection. Recent studies demonstrated that concurrent dual β-herpesvirus infections were an increased risk factor for "viral syndrome" and "CMV disease" development in patients undergoing renal transplantation [7,18,26]. HHV-7 reactivation precedes reactivation of CMV, and this virus can act as a helper virus for CMV and HHV-6 reactivation [7,18].…”

Association of HHV-6 and HHV-7 reactivation with the development of chronic allograft nephropathy

“…The kinetics of the activation of these viruses during the post-transplantation period suggest that HHV-7 may act as a co-factor for HHV-6 and CMV reactivation, while both HHV-6 and HHV-7 may act as co-factors in the pathogenesis of CMV disease and acute rejection. [12][13][14][15][16] The aim of this study was to determine HHV-6 and HHV-7 activation during the post-transplantation period and to evaluate the possible effects of the activation of these viruses on CAN development in renal transplant patients.…”

Detection of Human Herpesvirus-7 DNA in Bronchoalveolar Lavage

“…The direct manifestation of HHV-7 reactivation posttransplantation is poorly known [21,22] . Considering the relationship between viral reactivation related with ␤ -herpesviruses occurring after transplantation, several studies have evidenced the development of HCMV disease together with the concomitant reactivation of HHV-7, but its role is uncertain [22][23][24][25] , also taking into consideration the several host-and virus-related factors favoring the development of HCMV disease [26] . In a study on lung transplant recipients, Ross et al [6] evidenced an association between bronchiolitis obliterans (BO) with organizing pneumonia (BOOP) and HHV-7 DNA positivity in all 7 cases found in a group of 19 graft recipients, although viral load was not evaluated.…”