Experimental cross-species infection of common marmosets by titi monkey adenovirus - PubMed (original) (raw)

. 2013 Jul 24;8(7):e68558.

doi: 10.1371/journal.pone.0068558. Print 2013.

Shigeo Yagi, Ricardo Carrion Jr, Eunice C Chen, Maria Liu, Kathleen M Brasky, Robert E Lanford, Kristi R Kelly, Karen L Bales, David P Schnurr, Don R Canfield, Jean L Patterson, Charles Y Chiu

Affiliations

Experimental cross-species infection of common marmosets by titi monkey adenovirus

Guixia Yu et al. PLoS One. 2013.

Abstract

Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: This study was partly funded by an Abbott Viral Discovery Award. Charles Y. Chiu is the director of the UCSF-Abbott Viral Diagnostics and Discovery Center (VDDC) and Guixia Yu is employed by the VDDC. The University of California has also filed a patent application related to TMAdV (US Patent Application 20130034576A1). This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.

Figures

Figure 1

Figure 1. Whole-Genome Sequencing of Serially Passaged TMAdV.

(A) Genomic coverage of TMAdV by mapping of deep sequencing reads from a lung swab from a titi monkey with TMAdV pneumonia, passage 4 in A549 cells, and passage 10 in A549 cells. The coverage (y-axis) achieved at each position along the ∼37 kB TMAdV genome (x-axis) is plotted on a logarithmic scale. (B) Identification of single nucleotide polymorphisms (SNPs) in assembled TMAdV genomes. The coverage at each SNP position is shown in parentheses. SNP positions 14776A and 36545A (cyan lollipops) correspond to probable sequencing errors in the Sanger sequenced TMAdV genome (Genbank HQ913600). A 3202CG mutation is observed to occur between passage 4 (black lollipop) and passage 10 (red lollipop), which results in a 388PR amino acid coding change in the TMAdV E1B-55K protein. (C) A multiple sequence alignment of the E1B-55K protein of TMAdV and representative human and simian adenoviruses reveals that position 388 resides within a putative binding region for p53 and/or the MRE11-RAD50-NBS1 (MRN) complex. Human adenovirus type 5 (HAdV-5) mutants containing a nearby H534 insertion or mutations in the downstream C2H2 zinc finger inhibit binding to p53 and/or MRN .

Figure 2

Figure 2. Experimental TMAdV Infection in the Common Marmoset.

(A) Outline of TMAdV infection protocol and sample collections. The “[X]” refers to a marmoset that is sacrificed at the designated timepoint. (B) Results from PCR analysis of nasal swab samples collected at serial timepoints. Shown in parentheses are the calculated viral titers in genome copy numbers per mL associated with each timepoint. (C) Clinical scores in TMAdV-infected and control marmosets. The asterisks (*) refer to timepoints during which each infected marmoset exhibited the most pronounced clinical signs of illness (inset box). For a definition of the clinical scoring system, see Table S2. (D) Antibody titers in TMAdV-infected and control marmosets as measured using a TMAdV neutralization assay.

Figure 3

Figure 3. TMAdV-Associated Pathology in Experimentally Infected Marmoset CJ29019.

Histologic findings on necropsy tissue from day 15 post-inoculation include a mild bronchitis (A and B), enteritis (C and D), and an atypical nodular hyperplasia in the liver (E and F). The black rectangle in panels A, C, or E outlines the region magnified in panels B, D, or F, respectively.

Figure 4

Figure 4. TMAdV Antibody Staining of Titi and Marmoset Monkey Tissues.

Direct immunofluorescence staining of lung from two TMAdV-infected titi monkeys with fatal pneumonia (A-B, with corresponding magnified views in C-D) , and lung and liver from two TMAdV-inoculated marmosets (E-H) are shown. TMAdV staining is evident in lung from naturally infected titi monkeys who died from pneumonia, but absent in lung and liver from experimentally infected marmosets.

Similar articles

Cited by

References

    1. Harrach B, Benkö M, Both G, Brown M, Davis A, et al.. (2011) Family Adenoviridae. In: King A, Adams M, Carstens E, Lefkowitz E, editors. Virus Taxonomy: Classification and Nomenclature of Viruses Ninth Report of the International Committee on Taxonomy of Viruses. San Diego: Elsevier. 95–111.
    1. Lewis PF, Schmidt MA, Lu X, Erdman DD, Campbell M, et al. (2009) A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14. J Infect Dis 199: 1427–1434. - PubMed
    1. Wold W, Horwitz M (2007) Adenoviruses. In: Fields BN, Knipe DM, Howley PM, editors. Fields Virology. 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. 2395–2436.
    1. Prince GA, Porter DD, Jenson AB, Horswood RL, Chanock RM, et al. (1993) Pathogenesis of adenovirus type 5 pneumonia in cotton rats (Sigmodon hispidus). J Virol 67: 101–111. - PMC - PubMed
    1. Tsai JC, Garlinghouse G, McDonnell PJ, Trousdale MD (1992) An experimental animal model of adenovirus-induced ocular disease. The cotton rat. Arch Ophthalmol 110: 1167–1170. - PubMed

Publication types

MeSH terms

Grants and funding

LinkOut - more resources