Adenoviruses are DNA viruses that naturally infect many vertebrates, including humans and monkeys, and cause a wide range of clinical illnesses in humans. Infection from individual strains has conventionally been thought to be species-specific. Here we applied the Virochip, a pan-viral microarray, to identify a novel adenovirus (TMAdV, titi monkey adenovirus) as the cause of a deadly outbreak in a closed colony of New World monkeys (titi monkeys; Callicebus cupreus) at the California National Primate Research Center (CNPRC). Among 65 titi monkeys housed in a building, 23 (34%) developed upper respiratory symptoms that progressed to fulminant pneumonia and hepatitis, and 19 of 23 monkeys, or 83% of those infected, died or were humanely euthanized. Whole-genome sequencing of TMAdV revealed that this adenovirus is a new species and highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses. Cultivation of TMAdV was successful in a human A549 lung adenocarcinoma cell line, but not in primary or established monkey kidney cells. At the onset of the outbreak, the researcher in closest contact with the monkeys developed an acute respiratory illness, with symptoms persisting for 4 weeks, and had a convalescent serum sample seropositive for TMAdV. A clinically ill family member, despite having no contact with the CNPRC, also tested positive, and screening of a set of 81 random adult blood donors from the Western United States detected TMAdV-specific neutralizing antibodies in 2 individuals (2/81, or 2.5%). These findings raise the possibility of zoonotic infection by TMAdV and human-to-human transmission of the virus in the population. Given the unusually high case fatality rate from the outbreak (83%), it is unlikely that titi monkeys are the native host species for TMAdV, and the natural reservoir of the virus is still unknown. The discovery of TMAdV, a novel adenovirus with the capacity to infect both monkeys and humans, suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks.
Author Summary
Infection from adenoviruses, viruses that cause a variety of illnesses in humans, monkeys, and other animals, has conventionally been thought to be species-specific. We used the Virochip, a microarray designed to detect all viruses, to identify a new species of adenovirus (TMAdV, or titi monkey adenovirus) that caused a deadly outbreak in a colony of New World titi monkeys at the California National Primate Research Center (CNPRC), and also infected a human researcher. One-third of the monkeys developed pneumonia and liver inflammation, and 19 of 23 monkeys died or were humanely euthanized. The unusually high death rate (83%) makes titi monkeys unlikely to be natural hosts for TMAdV, and the genomic sequence of TMAdV revealed that it is very different from any other known adenovirus. The researcher developed an acute respiratory illness at the onset of the outbreak, and was found to be infected by TMAdV by subsequent antibody testing. A clinically ill family member with no prior contact with the CNPRC also tested positive. Further investigation is needed to identify whether TMAdV originated from humans, monkeys, or another animal. The discovery of TMAdV suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks.
