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Novel adenovirus jumps from monkey to scientist, causing serious illness

alert

Senior Moderator
http://www.businessweek.com/lifestyle/content/healthday/644823.html

New Virus 'Jumps' From Monkey to Scientist, Causing Serious Illness
Adenovirus strain is under study but experts say there's no immediate cause for alarmBy Jenifer Goodwin
HealthDay Reporter

FRIDAY, Oct. 22 (HealthDay News) -- A never-before detected strain of virus that killed more than one-third of a monkey colony at a U.S. lab appears to have 'jumped' from the animals to sicken a human scientist, researchers report.

Although it's an unusual move for that type of virus and does warrant further monitoring, the researchers stress there is no cause for alarm at this time. There is no evidence the virus has spread beyond the single scientist -- who recovered from her illness -- nor is there even proof that the virus would be transmissible between humans.

Still, "there is very strong evidence to suggest a cross-species transmission event happened," said lead investigator Dr. Charles Chiu, an assistant professor of laboratory medicine and medicine/infectious diseases at the University of California San Francisco. "I don't think people should be worried about this right now. It's more of a worry to public health officials monitoring these new viruses that have the potential for causing outbreaks."

The study was presented Friday at the Infectious Diseases Society of America annual meeting in Vancouver, Canada.

The scientist appears to have caught the virus while investigating an outbreak of illness among a colony of Titi monkeys at the California National Primate Research Center in Davis, Chiu said.

Among the monkeys, the virus was highly contagious and deadly: Of 55 monkeys housed at the center, 23 (about 40 percent) became seriously ill with upper respiratory symptoms that progressed to pneumonia and an inflammation of the liver. Nineteen monkeys, or about 83 percent of those infected, died.

Broad-spectrum antibiotics did not help the monkeys, suggesting that the pneumonia was caused by the virus and not a secondary bacterial infection, Chiu said.

Researchers later determined the cause of the illness was an adenovirus, a broad class of viruses that can cause everything from relatively harmless respiratory illnesses such as the common cold, to pneumonia, as well as gastroenteritis, conjunctivitis and inflammation of the liver in people.

The new strain, however, had never before been identified, Chiu said.

"This is almost certainly a new species of adenovirus," Chiu said. "By looking at the 'sequence divergence', or how different the genetic sequence of this adenovirus is relatively to other adenoviruses, we believe it is a new species."

The scientist who fell ill had been in close contact with the monkeys. Though she became seriously ill with pneumonia around the same time the monkeys were falling ill, she was not hospitalized and recovered after about four weeks, Chiu said.

Her blood tested positive for antibodies to the virus three months after the epidemic, Chiu said. While not a definitive test, Chiu said it's very likely the cause of her illness was the new adenovirus
.

Infectious disease and public health experts are always on the lookout for new viruses that pose a threat to people, said Dr. Aaron Glatt, a spokesman for the Infectious Diseases Society of America and president and CEO of St. Joseph Hospital in Bethpage, N.Y.

While this sort of event makes infectious disease experts sit up and take notice, "it's not something to be nervous about or worried about today," Glatt said. "There is not a novel adenovirus associated with a deadly outbreak in humans, but it's very interesting from a scientific point of view."

While other viruses can infect more than one species, adenoviruses tend to be species-specific, which makes this somewhat unusual, he said. But as of now, there is no evidence of an outbreak of the virus outside that single monkey colony in Davis, Glatt added.

Chiu and his colleagues are trying to determine the origin of the virus, including whether it started as a monkey virus or began in a human and was passed to the monkeys. Since no new monkeys had been introduced to the colony in six years, one possibility is that the virus was circulating, undetected, in rhesus monkeys also housed at the facility and passed somehow to the Titis.

Researchers are also screening several thousand people to determine if anyone else has antibodies to the virus, which would indicate prior exposure and that the virus has already been in circulation in the general human population.

Another question is whether it's contagious among people, Chiu said. "There is possibly some evidence it's transmissible, but we just don't know yet," Chiu noted. "If this virus has the potential for human-to-human transmission, it would have the potential of developing into an outbreak."

While adenoviruses usually stick to one species, other viruses do "jump" between species frequently, Chiu said, and a virus that makes one species very ill may be relatively harmless in another.

SARS coronavirus, for example, colonizes bats and ferrets without causing disease, while in humans the illness triggers severe pneumonia, Chiu said.

Influenza also jumps between species. Pigs may show no signs of having H1N1 ("Swine flu"), but humans can get very sick from it.

Researchers are also working to determine if the new adenovirus is a "recombinant," or combined virus, which includes bits of genetic information from monkey and human adenoviruses.

"When viruses jump they can cause much more severe disease or less severe disease," Chiu said. "These findings might be an argument to do more broad surveillance of animals. If we can better understand what kind of viruses circulate in animals, it might help predict what viruses might jump over and when."
 
Re: Novel adenovirus jumps from monkey to scientist, causing serious illness

http://www.idmeeting.org/files/1098/196.pdf

196. Identification of a Novel Adenovirus Associated with a Deadly Outbreak in
a Titi Monkey Colony
Presenter: Charles Y. Chiu, M.D./Ph.D. , Laboratory Medicine and Medicine / Infectious Diseases,
University of California, San Francisco, San Francisco, CA
Background: Adenoviruses are DNA viruses that cause a broad spectrum of diseases in humans,
including respiratory tract infections, gastroenteritis, conjunctivitis, and hepatitis. Infection from
adenoviruses is thought to be highly species‐specific.
Methods: The Virochip, a DNA microarray designed to detect all known and novel viruses on the basis of
conserved sequence homology, was used to investigate the cause of an outbreak among a group of Titi
monkeys at the California National Primate Research Center in Davis, California. Affected monkeys first
developed upper respiratory symptoms that rapidly progressed into severe pneumonia and hepatitis.
Of the 60 monkeys housed at the center, 23 monkeys became extremely ill and ultimately 19 died (83%
mortality rate) despite aggressive medical treatment. Necropsies of lung and liver tissue revealed acute
destruction of the parenchyma; histological examination revealed the presence of intranuclear
inclusions. Routine microbiological testing was negative.
Results: Tissue and swab samples from infected animals revealed the signature of an adenovirus on
Virochip. Sequencing of the nearly complete 35k genome revealed that the adenovirus was divergent
and a member of a new group, sharing only 80‐85% overall nucleotide identity with its closest relatives.

The adenovirus was culturable on both human A549 and monkey BSC‐1 and RMK cells, but grew best in
human A549 cell lines. Serological analysis by virus neutralization revealed strong antibody responses in
affected monkeys who survived the outbreak but not in negative controls. An investigator at the center
in close contact with the Titi monkeys developed a severe pneumonia at the onset of the outbreak. Her
convalescent serum collected 6 months later was seropositive for the adenovirus, strongly implicating a
cross‐species transmission event.

Conclusion: A novel adenovirus was identified as the cause of a deadly outbreak of pneumonia and
hepatitis in a Titi monkey colony, and also appeared to have infected a human. To our knowledge, this is
the first example of a cross‐species transmission event from adenovirus infection. Further studies are
ongoing to establish whether the virus is of simian or human origin
 
Re: Novel adenovirus jumps from monkey to scientist, causing serious illness

http://dels-old.nas.edu/ilar_n/ilarjournal/49_2/pdfs/v4902Roberts.pdf
ILAR Journal Volume 49, Number 2 2008
Nonhuman Primate Quarantine: Its Evolution and Practice

Jeffrey A. Roberts and Kirk Andrews
[snip]
The importation of nonhuman primates continues to represent a critical element in meeting research needs for NHP models. The number of animals imported has increased steadily over the past 4 years and will continue to expand to meet research needs in areas such as genetics, infectious disease, and neuroscience (Mullan 2006; Robinson and Beattie 2003). But the exclusion of animals with latent viral or even bacterial infections that are not health risks may limit the availability of certain populations or species and complicate effective genetic management of domestic breeding colonies.
The use of primary quarantine to prevent the introduction
of disease-causing agents is an appropriate and valuable
step in protecting human health as well as the health of both research and breeding colonies. And while the goal of the CDC regulations is to protect public health, the regulations and infection control programs that have developed in response to the CDC requirements have also dramatically reduced morbidity and mortality of animals during shipment and upon their arrival at quarantine facilities.
The biggest challenges now facing nonhuman primate importation are the need for improved diagnostic tools to screen for diseases such as tuberculosis and the ability to respond rapidly when a new agent is identified. The 2003 SARS outbreak in China disrupted the international NHP supply when the Chinese government, in an effort to control the outbreak, banned all animal movement. Primate exports resumed after surveys of animal handlers and the species they worked with implicated the palm civet as a primary source of infection (CDC 2003b).
The continued demand for nonhuman primates increases
the likelihood that new unknown agents will be identified.
The best response to such an occurrence will be the continued rigorous application of the lessons learned about nonhuman primate quarantine over the past 60 years.

Maybe a mandatory quarantine of exposed humans who get ill at the same time a serious illness afflicts a lab animal colony would be a good idea.
 
Re: Novel adenovirus jumps from monkey to scientist, causing serious illness

Reading this case report, the adenovirus affecting the Titi's is very, very unusual if they are healthy monkeys.

http://vp4.afip.org/wsc/wsc06/06wsc19.pdf
The Armed Forces Institute of Pathology
Department of Veterinary Pathology

WEDNESDAY SLIDE CONFERENCE
2006-2007
CONFERENCE 19
14 March 2007
In immunocompromised monkeys simian adenovirus is an uncommon, but significant potential opportunistic pathogen and has been associated with
segmental enteritis involving the ileum and necrotizing pancreatitis in SIV infected rhesus macaques.4,5,6 Necrotizing hepatitis is an extremely rare manifestation of adenovirus infection in nonhuman primates. Individual cases have been described in rhesus monkeys (Macaca mulatta, African green monkeys (Cercopithecus aethiops) and chimpanzees (Pan troglodytes) that all showed evidence of immunosuppression.7
In the present case etiological diagnosis of adenoviral hepatitis was based on transmission electron microscopy with evidence of paracrystalline arrays of
adenovirus in the nucleus of hepatocytes (Fig. 1).
Other causes of necrotizing hepatitis in rhesus monkeys include hepatitis A and hepatitis B, SV40 and herpesvirus infection. In domestic animals adenoviruses
have been recovered from cattle, sheep, pigs, horses, mice and dogs and are most often associated with pneumonia and enteritis. However, with the exception of
infectious canine hepatitis, most are not serious causes of disease in animals other than those that are immunocompromised.
1
 
Re: Novel adenovirus jumps from monkey to scientist, causing serious illness

http://www.promedmail.org/pls/apex/..._BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,85465

Archive Number 20101023.3850
Published Date 23-OCT-2010
Subject PRO/AH/EDR> Novel pneumonia-associated adenovirus, Titi monkey, human

NOVEL PNEUMONIA-ASSOCIATED ADENOVIRUS, TITI MONKEY, HUMAN
*********************************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

******
(1) Press report
Date: Fri 22 Oct 2010
Source: Bloomberg Businessweek, HealthDay News [edited]
<http://www.businessweek.com/lifestyle/content/healthday/644823.html>



New Virus 'Jumps' From Monkey to Scientist, Causing Serious Illness
-------------------------------------------------------------------
A never-before detected strain of virus that killed more than one-3rd
of a monkey colony at a U.S. laboratory appears to have 'jumped' from
the animals to sicken a human scientist, researchers report. Although
it's an unusual move for that type of virus and does warrant further
monitoring, the researchers stress there is no cause for alarm at
this time. There is no evidence the virus has spread beyond the
single scientist -- who recovered from her illness -- nor is there
even proof that the virus would be transmissible between humans.

Still, "there is very strong evidence to suggest a cross-species
transmission event happened," said lead investigator Dr. Charles
Chiu, an assistant professor of laboratory medicine and
medicine/infectious diseases at the University of California San
Francisco. "I don't think people should be worried about this right
now. It's more of a worry to public health officials monitoring these
new viruses that have the potential for causing outbreaks."

The study was presented on Friday [22 Oct 2010] at the Infectious
Diseases Society of America annual meeting in Vancouver, Canada. The
scientist appears to have caught the virus while investigating an
outbreak of illness among a colony of Titi monkeys at the California
National Primate Research Center in Davis, Chiu said.

Among the monkeys, the virus was highly contagious and deadly: Of 55
monkeys housed at the center, 23 (about 40 percent) became seriously
ill with upper respiratory symptoms that progressed to pneumonia and
an inflammation of the liver. A total of 19 monkeys, or about 83
percent of those infected, died. Broad-spectrum antibiotics did not
help the monkeys, suggesting that the pneumonia was caused by the
virus and not a secondary bacterial infection, Chiu said.

Researchers later determined the cause of the illness was an
adenovirus, a broad class of viruses that can cause everything from
relatively harmless respiratory illnesses such as the common cold, to
pneumonia, as well as gastroenteritis, conjunctivitis and
inflammation of the liver in people.

The new strain, however, had never before been identified, Chiu said.
"This is almost certainly a new species of adenovirus," Chiu said.
"By looking at the 'sequence divergence,' or how different the
genetic sequence of this adenovirus is relatively to other
adenoviruses, we believe it is a new species."

The scientist who fell ill had been in close contact with the
monkeys. Though she became seriously ill with pneumonia around the
same time the monkeys were falling ill, she was not hospitalized and
recovered after about 4 weeks, Chiu said. Her blood tested positive
for antibodies to the virus 3 months after the epidemic, Chiu said.
While not a definitive test, Chiu said it's very likely the cause of
her illness was the new adenovirus.

Infectious disease and public health experts are always on the
lookout for new viruses that pose a threat to people, said Dr. Aaron
Glatt, a spokesman for the Infectious Diseases Society of America and
president and CEO of St. Joseph Hospital in Bethpage, N.Y. While this
sort of event makes infectious disease experts sit up and take
notice, "it's not something to be nervous about or worried about
today," Glatt said. "There is not a novel adenovirus associated with
a deadly outbreak in humans, but it's very interesting from a
scientific point of view." While other viruses can infect more than
one species, adenoviruses tend to be species-specific, which makes
this somewhat unusual, he said. But as of now, there is no evidence
of an outbreak of the virus outside that single monkey colony in
Davis, Glatt added.

Chiu and his colleagues are trying to determine the origin of the
virus, including whether it started as a monkey virus or began in a
human and was passed to the monkeys. Since no new monkeys had been
introduced to the colony in 6 years, one possibility is that the
virus was circulating, undetected, in rhesus monkeys also housed at
the facility and passed somehow to the Titis.

Researchers are also screening several thousand people to determine
if anyone else has antibodies to the virus, which would indicate
prior exposure and that the virus has already been in circulation in
the general human population. Another question is whether it's
contagious among people, Chiu said. "There is possibly some evidence
it's transmissible, but we just don't know yet," Chiu noted. "If this
virus has the potential for human-to-human transmission, it would
have the potential of developing into an outbreak."

While adenoviruses usually stick to one species, other viruses do
"jump" between species frequently, Chiu said, and a virus that makes
one species very ill may be relatively harmless in another. SARS
coronavirus, for example, colonizes bats and ferrets without causing
disease, while in humans the illness triggers severe pneumonia, Chiu
said. Influenza also jumps between species. Pigs may show no signs of
having H1N1 ("Swine flu"), but humans can get very sick from it.

Researchers are also working to determine if the new adenovirus is a
"recombinant," or combined virus, which includes bits of genetic
information from monkey and human adenoviruses. "When viruses jump
they can cause much more severe disease or less severe disease," Chiu
said. "These findings might be an argument to do more broad
surveillance of animals. If we can better understand what kind of
viruses circulate in animals, it might help predict what viruses
might jump over and when."

[Byline: Jenifer Goodwin]

--
Communicated by:
a correspondent requesting anonymity

******
[2] Meeting Abstract
Date: Fri 22 Oct 2010
Source: IDSA Meeting, Abstract 196: Oral Abstract Session: Virology [edited]
<http://idsa.confex.com/idsa/2010/webprogram/Paper3440.html>


Identification of a Novel Adenovirus Associated with a Deadly
Outbreak in a Titi Monkey Colony
----------------------------------------------------------------------------------------------
Background: Adenoviruses are DNA viruses that cause a broad spectrum
of diseases in humans, including respiratory tract infections,
gastroenteritis, conjunctivitis, and hepatitis. Infection from
adenoviruses is thought to be highly species-specific.

Methods: The Virochip, a DNA microarray designed to detect all known
and novel viruses on the basis of conserved sequence homology, was
used to investigate the cause of an outbreak among a group of Titi
monkeys at the California National Primate Research Center in Davis,
California. Affected monkeys 1st developed upper respiratory symptoms
that rapidly progressed into severe pneumonia and hepatitis. Of the
60 monkeys housed at the center, 23 monkeys became extremely ill and
ultimately 19 died (83 percent mortality rate) despite aggressive
medical treatment. Necropsies of lung and liver tissue revealed acute
destruction of the parenchyma; histological examination revealed the
presence of intranuclear inclusions. Routine microbiological testing
was negative.

Results: Tissue and swab samples from infected animals revealed the
signature of an adenovirus on Virochip. Sequencing of the nearly
complete 35k [base pair] genome revealed that the adenovirus was
divergent and a member of a new group, sharing only 80-85 percent
overall nucleotide identity with its closest relatives. The
adenovirus was culturable on both human A549 and monkey BSC-1 and RMK
cells, but grew best in human A549 cell lines. Serological analysis
by virus neutralization revealed strong antibody responses in
affected monkeys who survived the outbreak but not in negative
controls. An investigator at the center in close contact with the
Titi monkeys developed a severe pneumonia at the onset of the
outbreak. Her convalescent serum collected 6 months later was
seropositive for the adenovirus, strongly implicating a cross-species
transmission event.

Conclusion: A novel adenovirus was identified as the cause of a
deadly outbreak of pneumonia and hepatitis in a Titi monkey colony,
and also appeared to have infected a human. To our knowledge, this is
the 1st example of a cross-species transmission event from adenovirus
infection. Further studies are ongoing to establish whether the virus
is of simian or human origin.

--
Communicated by:
ProMED-mail
<promed@ promedmail.org>

[General information on the role of adenoviruses in human disease can
be found at:
<http://www.cdc.gov/ncidod/dvrd/revb/respiratory/eadfeat.htm>, and
photographs and information on Titi monkeys can be accessed at:
<http://www.northrup.org/photos/dusky-titi/>.

Neither of the above accounts clearly establishes the direction of
transmission of this novel pneumonia-associated adenovirus. The
information provided does not indicate whether this novel adenovirus
should be classified in the genus _Mastradenovirus_, together with
the numerous other human and simian adenovirus species previously
characterised, or whether it is a new adenovirus species that should
be ranked as the representative of an entirely new taxonomic genus.

Further characterisation of this novel adenovirus is awaited with
great interest, as are the outcomes of seroprevalence studies in the
human and Titi monkey population
in their natural environment (South
America). - Mod.CP]
...................cp/ejp/lm
 
Re: Novel adenovirus jumps from monkey to scientist, causing serious illness

Conclusion: A novel adenovirus was identified as the cause of a
deadly outbreak of pneumonia and hepatitis in a Titi monkey colony,
and also appeared to have infected a human.:magnify:
 
Re: Novel adenovirus jumps from monkey to scientist, causing serious illness

http://journals.lww.com/revmedmicrobiol/Abstract/2010/04000/Recombinant_adenovirus_type_3_and_type_14_isolated.2.aspx
Reviews in Medical Microbiology:
April 2010 - Volume 21 - Issue 2 - p 28?30
doi: 10.1097/MRM.0b013e3283393523
Recombinant adenovirus type 3 and type 14 isolated from a fatal case of pneumonia
Halstead, Diane C
Collapse Box
Abstract

We report a fatal case of pneumonia apparently due to adenovirus infection in a 53-year-old man who had recently returned from Iraq. The isolate was identified by sequence analysis as adenovirus type 3 and adenovirus type 14. On the basis of restriction enzyme analysis, the virus appeared to be a recombinant virus containing properties of both adenovirus type 3 and adenovirus type 14 rather than a co-infection with these two viruses.

? 2010 Lippincott Williams & Wilkins, Inc.
 
Last edited by a moderator:
Re: Novel adenovirus jumps from monkey to scientist, causing serious illness

Thanks for clarifying that, alert. (And that is very interesting about Ad14 being serious enough to have been confused with H5N1.)

I guess after reading more about Ad14, I was wondering if this what got into the primate center and evolved a bit. We have been hit pretty hard with Ad14 on the west coast. It does sound like the Titi's were ill prior to the scientist tending to them, though. The press release mentions a nearest relative but doesn't say which one, so that is confusing. If Ad14 is recombining with other adenoviruses, that might make things more confusing.

Dr. Chiu talks about the U.C. Davis outbreak on the Vancouver IDSA meeting video titled, What's the Next Big Problem?," hosted at the site below. (It is about 20:00 minutes into the video.)

http://www.medpagetoday.com/MultiMedia/MultiMedia/22881?ondemand=22881
 
Re: Novel adenovirus jumps from monkey to scientist, causing serious illness

Source: http://www.livescience.com/15061-monkey-killing-virus-sickens-lab-workers.html

Article:
Monkey-Killing Virus Sickens Lab Workers
Jennifer Welsh, LiveScience Staff Writer
Date: 14 July 2011 Time: 05:28 PM ET

An outbreak of a monkey-killing cold virus is the first example of an adenovirus that can infect both monkeys and humans.

Since they were discovered in the 1950s, researchers have thought each adenovirus strain could infect only one species of animal. One species of adenovirus might be able to infect only a hamster while another might infect only a cat. This is the first example of an adenovirus infecting two different types of animals, in this case, titi monkeys and lab-worker humans.

"Now adenoviruses can be added to the list of pathogens that have the ability to cross species," study researcher Charles Chiu, director of the viral diagnostics center at the University of California, San Francisco, said in a statement... [10 Deadly Diseases That Hopped Across Species]

************************************************************************

Source: http://esciencenews.com/articles/20...st.adenovirus.jump.between.monkeys.and.humans

UCSF confirms first adenovirus to jump between monkeys and humans
Published: Thursday, July 14, 2011 - 16:35 in Biology & Nature
Charles Chiu, MD, Ph.D. is a researcher at University of California - San Francisco.
Susan Merrell, UCSF

A novel virus that spread through a California monkey colony in late 2009 also infected a human researcher and a family member, UCSF researchers have found, the first known example of an adenovirus "jumping" from one species to another and remaining contagious after the jump. In a study by the UCSF Viral Diagnostics and Discovery Center, which identified the new virus at the time of the outbreak, researchers confirmed it was the same virus in the New World titi monkeys and the two humans. They also confirmed that the virus is highly unusual in both populations, suggesting that it may have originated from a third, unidentified species.

The direction in which the virus spread, however – from monkeys to humans or vice versa – remains a mystery.

Findings appear in the July 14 issue of PLoS Pathogens, a weekly journal of the Public Library of Science, and can be found at

http://www.plospathogens.org/articl.../NewArticles+(Ambra+-+Pathogens+New+Articles)
 
Last edited by a moderator:
PLoS Pathogens. Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony

PLoS Pathogens. Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony

[Source: PLoS Pathogens, full text: (LINK). Abstract, edited.]

Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony



Eunice C. Chen<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP>, Shigeo Yagi<SUP>3</SUP>, Kristi R. Kelly<SUP>4</SUP>, Sally P. Mendoza<SUP>4</SUP>, Nicole Maninger<SUP>4</SUP>, Ann Rosenthal<SUP>4</SUP>, Abigail Spinner<SUP>4</SUP>, Karen L. Bales<SUP>4</SUP><SUP>,</SUP><SUP>5</SUP>, David P. Schnurr<SUP>3</SUP>, Nicholas W. Lerche<SUP>4</SUP>, Charles Y. Chiu<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>,</SUP><SUP>6</SUP><SUP>*</SUP>

1 Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America, 2 UCSF-Abbott Viral Diagnostics and Discovery Center, University of California San Francisco, San Francisco, California, United States of America, 3 Viral and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, California, United States of America, 4 California National Primate Research Center, University of California Davis, Davis, California, United States of America, 5 Department of Psychology, University of California Davis, Davis, California, United States of America, 6 Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, California, United States of America



Abstract

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.


Citation: Chen EC, Yagi S, Kelly KR, Mendoza SP, Maninger N, et al. (2011) Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony. PLoS Pathog 7(7): e1002155. doi:10.1371/journal.ppat.1002155

Editor: Glen R. Nemerow, The Scripps Research Institute, United States of America

Received: January 20, 2011; Accepted: May 23, 2011; Published: July 14, 2011

Copyright: ? 2011 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work is supported in part by CNPRC NIH grant NCRR P51-RR000169, NIH grant HD053555 (to KLB, SPM, and WAM), NIH grants K08-AI074913 and R56-AI089532 (to CYC), and an Abbott Viral Discovery Award (to CYC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors received a viral discovery award from Abbott Diagnostics (to CYC). The University of California, San Francisco (UCSF) has also filed a patent application related to TMAdV. This does not alter the authors' adherence to all PloS Pathogens policies on sharing data and materials.
* E-mail: charles.chiu@ucsf.edu

- --------
 
Re: Novel adenovirus jumps from monkey to scientist, causing serious illness

http://motherjones.com/politics/1999/11/high-risk-monkey-business
High-Risk Monkey Business

The exotic-animal trade is moving disease-carrying primates from labs and zoos into the hands of pet owners. The results, scientists warn, can be deadly.

? By Alan Green

November/December 1999 Issue

[snip]
"If no one is performing up-front testing for zoonotic diseases," says Dr. Stephanie Ostrowski of the CDC, referring to diseases that can be passed from animals to humans, "then it's not a question of whether there's going to be a disastrous incident, but when." ....
 
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