title: Genomic stability of adipogenic human adenovirus 36.
abstract: Human adenovirus Ad36 increases adiposity in several animal models, including rodents and non-human primates. Importantly, Ad36 is associated with human obesity, which has prompted research to understand its epidemiology and to develop a vaccine to prevent a subgroup of obesity. For this purpose, understanding the genomic stability of Ad36 in vivo and in vitro infections is critical. Here, we examined whether in vitro cell passaging over a 14-year period introduced any genetic variation in Ad36. We sequenced the whole genome of Ad36-which was plaque purified in 1998 from the original strain obtained from American Type Culture Collection, and passaged approximately 12 times over the past 14 years (Ad36-2012). This DNA sequence was compared with a previously published sequence of Ad36 likely obtained from the same source (Ad36-1988). Compared with Ad36-1988, only two nucleotides were altered in Ad36-2012: a T insertion at nucleotide 1862, which may induce early termination of the E1B viral protein, and a T➝C transition at nucleotide 26 136. Virus with the T insertion (designated Ad36-2012-T6) was mixed with wild-type virus lacking the T insertion (designated Ad36-2012-T5) in the viral stock. The transition at nucleotide 26 136 does not change the encoded amino acid (aspartic acid) in the pVIII viral protein. The rate of genetic variation in Ad36 is ∼2.37 × 10(-6) mutations/nucleotide/passage. Of particular importance, there were no mutations in the E4orf1 gene, the critical gene for producing obesity. This very-low-variation rate should reduce concerns about genetic variability when developing Ad36 vaccines or developing assays for detecting Ad36 infection in populations.
authors.affiliation: Department of Biotechnology, Catholic University of Korea, Bucheon, Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Nam
authors.affiliation: Infections and Obesity Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
authors.forename: H-N
authors.initials: HN
authors.lastname: Na
authors.affiliation: Obetech Obesity Research Center, Richmond, VA, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Atkinson
authors.affiliation: Infections and Obesity Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
authors.forename: N V
authors.initials: NV
authors.lastname: Dhurandhar
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics* / Q000502:physiology; D050156:Adipogenesis; D050154:Adiposity / Q000502:physiology*; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism*; D014644:Genetic Variation; D042822:Genomic Instability / Q000235:genetics* / Q000502:physiology; D006801:Humans; D051379:Mice; D023421:Models, Animal; D011323:Primates; D012367:RNA, Viral / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D012367:RNA, Viral