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

Yu G, Yagi S, Carrion R, Chen EC, Liu M, Brasky KM, Lanford RE, Kelly KR, Bales KL, Schnurr DP, Canfield DR, Patterson JL, Chiu CY - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America.

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.

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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.
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pone-0068558-g002: 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.

Mentions: We examined TMAdV infectivity by inoculating marmosets intranasally with 0.1 mL of 105 TCID50/mL of P10 virus for which sufficient viral stocks were available. The inoculation dose (104 TCID50) was chosen to be similar to the physiologic doses used in experimental nasal inoculation of nonhuman primates at the TBRI with acute respiratory viruses such as RSV (respiratory syncytial virus). Three marmosets, CJ29012, CJ29019, and CJ29020, were inoculated with culture-adapted TMAdV (passage 13), while one marmoset, CJ29021, was inoculated with cell culture media as a control (Fig. 2A). All animals appeared normal until approximately 5 to 10 days after infection, when clinical signs presented in 3/3 inoculated monkeys (clinical scores >4) (Fig. 2C; Table S2). Animals exhibited reduced activity, had decreased stool production, became anorexic, and developed low-grade fevers. Marmoset CJ29012 demonstrated the most severe clinical signs and was in guarded physical condition with nasal congestion and sneezing by day 10. After day 11, all 3 experimentally infected animals recovered quickly, with marmosets CJ29019 and CJ29020 fully recovered at the time of euthanasia on day 15. To assess the effect of re-infection with TMAdV, marmoset CJ29012 was re-inoculated on day 15 and, along with control marmoset CJ29021, was observed for an additional 21 days prior to euthanasia at day 36. No clinical signs of infection were observed in marmoset CJ29012 (experimental TMAdV animal) or marmoset CJ29021 (experimental control animal) after re-inoculation (clinical scores < = 4).


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

Yu G, Yagi S, Carrion R, Chen EC, Liu M, Brasky KM, Lanford RE, Kelly KR, Bales KL, Schnurr DP, Canfield DR, Patterson JL, Chiu CY - PLoS ONE (2013)

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.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3722195&req=5

pone-0068558-g002: 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.
Mentions: We examined TMAdV infectivity by inoculating marmosets intranasally with 0.1 mL of 105 TCID50/mL of P10 virus for which sufficient viral stocks were available. The inoculation dose (104 TCID50) was chosen to be similar to the physiologic doses used in experimental nasal inoculation of nonhuman primates at the TBRI with acute respiratory viruses such as RSV (respiratory syncytial virus). Three marmosets, CJ29012, CJ29019, and CJ29020, were inoculated with culture-adapted TMAdV (passage 13), while one marmoset, CJ29021, was inoculated with cell culture media as a control (Fig. 2A). All animals appeared normal until approximately 5 to 10 days after infection, when clinical signs presented in 3/3 inoculated monkeys (clinical scores >4) (Fig. 2C; Table S2). Animals exhibited reduced activity, had decreased stool production, became anorexic, and developed low-grade fevers. Marmoset CJ29012 demonstrated the most severe clinical signs and was in guarded physical condition with nasal congestion and sneezing by day 10. After day 11, all 3 experimentally infected animals recovered quickly, with marmosets CJ29019 and CJ29020 fully recovered at the time of euthanasia on day 15. To assess the effect of re-infection with TMAdV, marmoset CJ29012 was re-inoculated on day 15 and, along with control marmoset CJ29021, was observed for an additional 21 days prior to euthanasia at day 36. No clinical signs of infection were observed in marmoset CJ29012 (experimental TMAdV animal) or marmoset CJ29021 (experimental control animal) after re-inoculation (clinical scores < = 4).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America.

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.

Show MeSH
Related in: MedlinePlus