A new zoonosis?July 15, 2011
Scientists in California have published in PLoS Pathogens their research on: Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony (see below for the link)
The paper details an outbreak of disease in a New World titi monkey colony at the California National Primate Research Centre (CNPRC) in 2009.
In May of that year lots of the titi monkeys started to get sick – the symptoms were coughing, lethargy and signs of respiratory distress like tachypnoea (fast breathing) and abdominal breathing. Gross pathology revealed the monkeys were getting pneumonia and in some cases hepatitis. Of the monkeys that got sick 83% died or had to be put to sleep.
A figure from the paper showing clinical and epidemiological features of the infection.
(A) Map of the titi monkey cages situated in one quadrant of a building, showing the locations of asymptomatic, at-risk monkeys (brown or green), affected surviving monkeys (black), and monkeys who died from their illness (skeleton). 3 monkeys were moved into the building (arrows pointing down and to the left) and 4 monkeys out of the building (arrows pointing up and to the right) during the 3rd week of the outbreak. The upper left photograph shows an image of an adult male titi monkey and his infant. The upper right inset shows the location of the titi monkey cages relative to other rhesus monkey cages in the building. Asymptomatic monkeys with positive serum antibody titers to TMAdV 4 months after the outbreak are shown in green. (B) Epidemic curve of the outbreak, with the number of cases in blue and cumulative attack rate in red. (C) Anteroposterior chest radiograph of an affected titi monkey, showing bilateral basilar infiltrates and a prominent right middle lobe consolidation. (D) 1 – gross photograph of lungs at necropsy; the lungs failed to fully collapse upon opening the chest, and a single ~1.5 cm focus of dark red discoloration (hemorrhage) can be seen in the left caudal lobe. 2 – photomicrograph of H&E stained lung tissue showing a severe diffuse necrotizing bronchopneumonia characterized by the presence of hemorrhage and intranuclear inclusions (arrows). 3 – photomicrograph of H&E stained liver tissue showing a multifocal necrotizing hepatitis with numerous intranuclear inclusions (arrows). 4 – transmission electron micrograph of an affected lung alveolus (scale bar = 1 µm) filled with adenovirus-like particles (inset, scale bar = 0.1 µm).
Researchers took samples from the sick and dead monkeys and tried to identify the cause of the disease. One of the techniques they used was the ‘virochip’ which is a microarray containing ~19 000 probes derived from all of the viral species in GenBank (~2 500).
Basically the microarry works by having single stranded nucleotide ‘probe’ sequences bound to different areas of a solid base (e.g. in a grid format). When a sample is added, nucleotide sequences complementary to the sequences on the microarray pair with them. The microarry chip is washed, removing unbound sequences. Fluorescence labelling of the sample nucleotide sequences allows researchers to see which of the probe sequences are now double stranded and the intensity of the fluorescence can be used to determine how strong the pairing is (effectively, what proportion of the bases in the sequence are paired).
The authors of this paper using this virochip in combination with their knowledge as to what groups of viruses cause pneumonia symptoms strongly suspected that the virus causing the outbreak was an adenovirus.
They then took the DNA sequences they had isolated from infected monkeys’ lungs, amplified a fragment of one of the genes and compared the sequence to other adenoviruses and found the viruses closest known relatives were an Old World vervet monkey adenovirus and the human species D adenoviruses.
They fully sequenced the virus and called it Titi Monkey Adenovirus (TMAdV).
They also did other cool work like growing it in a human cell line (although they couldn’t grow it in their monkey cell lines) and if you’re interested it’s definitely worth checking the paper out but what got me hooked on the story (other than the cute monkey pictures!) was the next bit…
One of the researchers reported becoming ill during the outbreak. They suffered from a fever, chills, headaches and described it feeling like ‘a burning sensation in the lungs’. Two of the researcher’s family members also had respiratory symptoms, although they were milder than the researcher’s. The family members never had contact with the monkeys. 4 months after the oubtreak the researcher had neutralising antibodies against the virus in their serum and one of the family members had neutralising antibodies in their serum a year later. None of the other researchers had any neutralising antibodies 4 months after the outbreak. Interestingly they tested the serum from 81 random blood donors in the Western USA and found two individuals with weakly neutralising antibodies, suggesting they had also come into contact with the virus somehow.
But what do all these results mean?
The researchers suggest that the severity of the disease suggests that the monkeys were not the natural reservoir for the virus. They don’t yet know what the reservoir is.
They also suggest that the virus spread from the monkeys to the researcher and not vice versa because:
- TMAdV’s closest relative is an Old World monkey adenovirus
- TMAdV can be picked up by PCR assays for human adenoviruses so if it was human in origin it would most likely have been identified before now
- GenBank contains loads more human adenoviruses than monkey viruses. It is highly likely that there are a lot of primate adenoviruses we haven’t discovered yet.
but they do not rule out that it could have gone from the human to the monkeys.
A lot more work is now needed to learn more about the virus, its reservoir, and its potential to cross species barriers.
I will definitely be keeping an eye/ear out for more news of TMAdV…
DNA microarray: Thanks to Guillaume Paumier for releasing it under the Creative Commons Attribution-Share Alike 3.0 unported licence
Titi monkeys with tails intertwined: Thanks to Steven G Johnson for releasing it under the Creative Commons Attribution-Share Alike 3.0 unported licence
Wang, D. (2002). Microarray-based detection and genotyping of viral pathogens Proceedings of the National Academy of Sciences, 99 (24), 15687-15692 DOI: 10.1073/pnas.242579699
Chen, E., Yagi, S., Kelly, K., Mendoza, S., Maninger, N., Rosenthal, A., Spinner, A., Bales, K., Schnurr, D., Lerche, N., & Chiu, C. (2011). Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony PLoS Pathogens, 7 (7) DOI: 10.1371/journal.ppat.1002155