Sequence typing of adenovirus from samples from hematological stem cell transplant recipients

Abstract

Adenovirus infections are usually mild or even asymptomatic, but infections with the virus are being recognized increasingly as a major cause of mortality and morbidity in the immunocompromised, particularly hematological stem cell transplant patients where infections can be life threatening and mortality may reach 60%. Typing by sequencing the HVR7 region of the hexon was established and validated using 60 isolates of different serotypes from the six of the seven species which had been typed previously by serum neutralization. Analysis of nucleotide sequences was used to type 227 samples from 41 hematological stem cell transplant recipients. Types from six species were detected but species C types were detected in 51.4% and species A in 34.3% of patients. Seven patients were infected with different adenovirus types sequentially and a further six patients had evidence of simultaneous multiple infections. Many of the sequences had several differences from the prototype strains which will allow tracing of outbreaks and provide evidence for cross-infection in a hospital setting. In this study, the phylogenetic analysis of adenovirus sequences from hematological stem cell transplant patients' samples showed evidence of two possible cross-infection incidents involving three and five patients, respectively.

Sequencing and phylogenetic analysis of the hexon, fiber, and penton regions of adenoviruses isolated from AIDS patients

“…Several of the isolates have the prototype sequence in the L2 region but the others have varying degrees of divergence from the prototype sequence, some resulting in amino acid changes. For example, Ad12v2 (Aids11) isolated in 1994 showed 15 nucleotide changes resulting in two amino acid changes and this variant has since appeared in hematological stem cell transplant patients from Manchester between 2004 and 2006 [Al Qurashi et al, 2011]. Similarly, some of the species D variants (Ad9v1, Ad20v1, Ad23v1, Ad26v1‐3) also have nucleotide changes that have resulted in amino acid changes (Table I).…”

Molecular evolution of human adenoviruses

“…Therefore, existing HAdV-Ds represent an evolutionary sampling of potential diversity, and proteotype analysis defines the available recombination palette of hypervariable regions for the evolution of new HAdV-Ds. It is also important to note that the evolution of new HAdVs by homologous recombination requires co-infection in the same host cell of at least two unique genotypes from the same viral species36373839404142. The emergence of new HAdV-Ds during the AIDS epidemic suggests a role for persistence of multiple viruses under reduced immune surveillance434445.…”

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

“…The adenoviruses most commonly reported to be associated with human disease worldwide are HAdV-C1, -C2, -C5, -B3, -B7, -B21, -E4, and -F41 (20,(62)(63)(64)(65)(66). In immunocompromised patients in the transplant setting, some of the most commonly reported adenovirus types include HAdV-C1, -C2, -C5, -A12, -A31, -B3, -B11, -B16, -B34, and -B35, with a strong predominance of species C in most instances (67)(68)(69)(70). For example, in the transplant unit of St. Anna Children's Hospital, Vienna, Austria, HAdV species C accounts for about 80% of all adenoviral infections observed, and similar numbers were also reported from other transplant centers in different geographic regions (43,69,(71)(72)(73).…”