Stability of human cytomegalovirus genotypes in persistently infected renal transplant recipients

Although most genes are highly conserved among strains of human cytomegalovirus (HCMV), several are unusually variable. By analyzing the sequence of two variable genes (UL146 and UL74) amplified directly from whole blood DNA extracts, multiple HCMV strains were detected in blood samples from 5/11 virus-infected renal transplant patients. These five patients were seronegative prior to transplantation and their likely acquisition of the virus was via the donated organ; HCMV-positive immunocompetent donors may thus be capable of harboring and transmitting multiple virus genotypes. In sequential samples taken up to 140 days post transplant no mutations in either gene were detected from 9/10 patients, and in the remaining patient a single nucleotide change was detected in UL146, and none in UL74. All sequences grouped into previously defined genotypes, with the detection of multiple members of the UL74 group 5 genotype establishing this previously tentative genotype. Additionally, identical sequences were identified in viruses from different patients, including examples from geographically distinct regions. Thus, although UL146 and UL74 exhibit impressive variation among strains, their sequences are maintained stably within and between infected individuals, suggesting that sequence differences between genotypes may be driven by differing gene function

Characterization and manipulation of the human adenovirus 4 genome

Human adenovirus 4 (HAdV-4), the only serotype of the species HAdV-E to be isolated from man, was first identified by its association with outbreaks of acute respiratory disease in military recruits. To combat such outbreaks, a live, oral HAdV-4 vaccine that is delivered via an enteric-coated capsule was developed. This vaccine has been used for nearly 40 years and has been shown to be safe and efficacious. In this study, the complete DNA sequence (35 994 bp) of the vaccine strain is described and its genetic content is analysed. Phylogenetic comparisons confirmed that the closest sequenced relative of HAdV-4 is another serotype of HAdV-E that infects chimpanzees (SAdV-25) and that the great majority of genes in HAdV-E are related most closely to HAdV-B genes. By using the sequence data, a system was constructed to facilitate production of replication-competent HAdV-4 recombinants

Development of targeted viral vectors for cardiovascular gene therapy

No abstract available