PCR detection and semiquantitative analysis of human cytomegalovirus (CMV), herpesvirus 6, and herpesvirus 7 infection following liver transplantation and interactions in the progression to CMV disease

Cytomegalovirus (CMV) is the most frequent cause of infection in liver transplant recipients. The new herpesviruses, HHV-6 and HHV-7, have been implicated as potential copathogens with CMV for the progression to CMV disease in the transplant recipients. In this study, a semiquantitative PCR assay was performed for the early diagnosis of human CMV, HHV-6, and HHV-7 infection in blood specimens (polymorphonuclear leukocytes) prospectively collected weekly for at least 8 weeks posttransplantation from a cohort of 43 consecutive liver transplant recipients not receiving anti-viral prophylaxis. These samples were tested for CMV, HHV-6 and HHV-7 DNA using primer sets directed to the CMV Hind III-X fragment region, HHV-6 major antigenic structural protein gene and HHV-7 U10, structural phosphoprotein (U11) genes, respectively. Results of PCR assays were correlated with recovery of CMV in cell culture, and histopathological findings from biopsy specimens of infected organs to assess clinical symptomatic and invasive CMV disease. DNAemia due to CMV, HHV-6 and HHV-7 was found in 65%, 32% and 44% of the patients, respectively at some time during the posttransplant period. CMV disease developed in 14 patients (32%), 6 (43%) of whom had coinfection with HHV-6 and 10 (71%) with HHV-7. Organ involvement with CMV developed in 9 of the 14 (64%) patients with CMV disease, 8 of whom had coinfection with the other herpesviruses; 5 with HHV-6, six with HHV-7, and 3 of the 8 patients had coinfection with HHV-6 and 7 at the same time. CMV disease was more common in the CMV D+/R- patients (85%) than in the other groups. Semiquantitative analysis showed higher levels of CMV, HHV-6, and HHV-7 DNA in patients with CMV disease than in asymptomatic patients. We conclude that in patients with CMV DNAemia, especially with high viral loads, concurrent infection with HHV-6, HHV-7 or both may be associated with an increased progression to CMV disease.