Genomic characterization of human adenovirus 36, a putative obesity agent

Abstract

Increased levels of serum antibody titers against human adenovirus 36 (HAdV-D36) are associated with human obesity and experimental obesity in laboratory animals. While HAdV-D36 has been studied as an infectious agent implicated in obesity for over a decade, the complete genome sequence and its analysis have yet to be reported. A detailed analysis of the genome sequence of HAdV-D36 may be important to understand its role in obesity. Genomic and bioinformatic comparisons with other HAdVs identified differences that suggested unique functions. Global pairwise genome alignment with all sequenced human adenovirus D (HAdV-D) genomes revealed areas of nonconserved sequences in the hexon, E3 CR1 beta, E3 CR1 gamma, and fiber genes. Phylogenetic analysis of all HAdV-D36 proteins confirmed that this virus belongs to species Human adenovirus D. This genomic analysis of HAdV-D36 provides an important tool for comprehending the role that this unique adenovirus may play in human obesity. Low amino acid sequence identity in the E3 CR1 beta and CR1 gamma genes may suggest distinctive roles for these proteins. Furthermore, the predicted molecular models of the HAdV-D36 fiber protein seem to implicate a unique tissue tropism for HAdV-D36.

Computational analysis and identification of an emergent human adenovirus pathogen implicated in a respiratory fatality

“…Human adenoviruses (HAdV) were first isolated in 1953 as respiratory pathogens (Hilleman and Werner, 1954; Rowe et al, 1953), and cause an array of human diseases including respiratory, gastrointestinal, renal, urinary tract, ocular surface infections, opportunistic infections in immune deficient individuals, and possibly obesity (Arnold et al, 2010; Chu and Pavan-Langston, 1979; Dhurandhar et al, 1992; Dingle and Langmuir, 1968; Kojaoghlanian, Flomenberg, and Horwitz, 2003; Wood, 1988). HAdVs cause infections in infancy and childhood, but are rarely diagnosed in neonates.…”

Molecular evolution of human species D adenoviruses

“…HAdV infections are readily transmittable and, in some cases, highly contagious. HAdVs infect multiple mucosal sites, including the gastrointestinal, respiratory, genitourinary, and ocular surfaces (Table 1) (Arnold et al, 2010; Chu and Pavan-Langston, 1979; Dingle and Langmuir, 1968; Wood, 1988). HAdVs have also been associated with obesity (Atkinson et al, 2005; Dhurandhar et al, 2000).…”

Infectivity period of mice inoculated with human adenoviruses

“…7– 9 While Ad36 has been a major research focus of our group, 1– 16 interest of other research groups in Ad36-related research is rapidly increasing globally, as indicated by several recent publications about Ad36 from other groups. 17 – 27 Therefore, in anticipation of increased use of animal models to investigate the effects of Ad36, we conducted the following experiments to determine the duration of infectivity of mice infected with Ad36 or Ad2. We determined infectivity of experimentally-infected mice, by tracking the duration of horizontal transmission to cage-mates.…”