A human rhinovirus in chimpanzees

rhinovirus receptors

Rhinovirus receptors

An outbreak of respiratory disease in Ugandan chimpanzees provides insight into how virus infection can shape the genome and lead to differences in the cell receptor gene that regulate susceptibility to infection.

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The AIDS pandemic

Origin of HIV

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Great ape protection act

chimpanzee HamI received the following email today from Judith S. Bond, President of the Federation of American Societies for Experimental Biology (FASEB):

Dear Colleague,

We need your help to counter a serious threat to the humane use of animals in research. The Great Ape Protection and Cost Savings Act (S 810), which would prohibit the use of chimpanzees in medical research, may be voted on in the Senate this week (it was approved by a Senate committee in July)! Passage of this bill could have devastating consequences for ongoing research into human diseases such as hepatitis C, as well as studies benefiting the great apes themselves. Even if you do not work with great apes, you should be concerned about this bill because it would end research deemed by the Institute of Medicine (IOM) to be ethically sound and scientifically important and could pave the way for legislation to ban research with other species

Those who oppose the use of animals in research are making an aggressive effort to get this bill passed before Congress goes home for the year. We must let them know that chimpanzees are important animal models for research. Please take action now by going to http://capwiz.com/faseb/issues/alert/?alertid=62215781 to send an email to your Senators urging them to oppose the Great Ape Protection and Cost Savings Act.

You can find the text of this bill on this webpage (the pdf link at the top of the page provides the most readable version of the bill). Great apes include the chimpanzee, bonobo, gorilla, orangutan, and gibbon. Invasive research is any research that may cause death, injury, pain, distress, fear, or trauma.

According to the text of the bill, the chimpanzee is the only great ape used for invasive research in the United States, where there are approximately 1000 housed in laboratories.

The bill cites the Institute of Medicine and National Research Council report entitled “Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity” which concluded that most current use of chimpanzees for biomedical research is unnecessary.  It states that research on hepatitis C antiviral drugs, respiratory syncytial virus, future monoclonal antibody therapies, or a therapeutic hepatitis C virus vaccine, does not require chimpanzees, and that ‘the use of a combination of non-chimpanzee methods for the development of monoclonal antibody therapies may make research on the chimpanzee largely unnecessary; and non-chimpanzee models, if further improved, may reduce or obviate the need for the continued use of the chimpanzee for prophylactic hepatitis C vaccine research.’

Presumably the authors of the bill refer in part to work directed on developing a mouse model for HCV infection. However, as indicated by the bill’s language, it is not yet clear if these models will supplant the chimpanzee for HCV research.

The purpose of this act is to phase out invasive research on great apes and the use of Federal funding of that research, both in and outside of the United States. All existing chimpanzee protocols must be terminated within three years of passing of the bill, and once the bill has been passed, no new chimpanzee experiments may be started.

There is an escape clause – if, after three years have passed, it is determined that a new disease requires research on chimpanzees, the Great Ape Task Force will be created to evaluate that need.

If this act had been passed in the 1950s, it might not have been possible to develop poliovirus vaccines. While transgenic mice recapitulate much of poliovirus pathogenesis, they are not orally susceptible to infection (unless the interferon system is disabled) and therefore cannot reliably be used to test protection conferred by immunization.

It seems premature to pass an act banning research on chimpanzees. These animals are needed for testing anti-HCV therapies and vaccines, and as stated in the bill, it is not yet clear if other animal models will replace chimpanzees. It seems prudent to wait until we have a suitable animal model for HCV (and other infectious and non-infectious diseases which currently require chimpanzees) before outlawing the use of this animal in research.

Reverse zoonoses: Human viruses that infect other animals

bonoboThe many human viral diseases that have crossed from other animal species  – such as AIDS, Ebola, SARS, encephalitis and respiratory diesease caused by henipaviruses – demonstrate the pathogenic potential of the zoonotic pool. Are there also reverse zoonoses – diseases of humans that are transferred to other animal species?

An example of a reverse zoonosis occurred just last week at Lincoln Park Zoo in Chicago, where a 9 year old chimpanzee died of respiratory disease caused by human metapneumovirus. This member of the paramyxovirus family is responsible for approximately 10% of all respiratory tract infections. All seven members of a group of chimpanzees were infected with the virus, but only one became ill. The virus was likely transmitted to the chimps by humans, but precisely how and when is not known. Outbreaks of fatal respiratory disease in wild chimpanzees have been reported previously, and human metapneumovirus has been one of several human viruses isolated from these primates. Such infections are expected to occur more frequently in zoological parks, and ando also in game preserves as human encroachment of these facilities increases.

Influenza virus may also be frequently transmitted from humans to other animal species. An outbreak of influenza recently lead to the death of 6 bonobos (a species of chimpanzee) in a Congo wildlife sanctuary. Although the influenza subtype responsible for the outbreak has not been identified, it has been suggested that the source was one or more visitors during the February epidemic of influenza in Kinshasha.

Human influenza viruses are frequently isolated from pigs. Since its emergence in 1968, the H3N2 subtype has infected pigs many times throughout the world, and has often caused serious outbreaks. More recently the influenza H1N1 subtype has been shown to infect pigs. Influenza viruses remain in the pig population for long periods of time, and may serve as reservoirs for the recycling of older influenza virus strains back into the human population.

Just as increasing human population, travel, and the global food business increase the likelhood that viruses will jump from animals into humans, the same factors ensure the reverse spread as well – often with dire consequences for zoological parks and wild and domestic animals. And the viruses we pass on may come back to haunt us another day.

Kaur, T., Singh, J., Tong, S., Humphrey, C., Clevenger, D., Tan, W., Szekely, B., Wang, Y., Li, Y., Alex Muse, E., Kiyono, M., Hanamura, S., Inoue, E., Nakamura, M., Huffman, M., Jiang, B., & Nishida, T. (2008). Descriptive epidemiology of fatal respiratory outbreaks and detection of a human‐related metapneumovirus in wild chimpanzees at Mahale Mountains National Park, Western Tanzania. American Journal of Primatology, 70 (8), 755-765 DOI: 10.1002/ajp.20565

Yu, H., Zhou, Y., Li, G., Zhang, G., Liu, H., Yan, L., Liao, M., & Tong, G. (2009). Further evidence for infection of pigs with human-like H1N1 influenza viruses in China Virus Research, 140 (1-2), 85-90 DOI: 10.1016/j.virusres.2008.11.008

de Jong, J., Smith, D., Lapedes, A., Donatelli, I., Campitelli, L., Barigazzi, G., Van Reeth, K., Jones, T., Rimmelzwaan, G., Osterhaus, A., & Fouchier, R. (2007). Antigenic and Genetic Evolution of Swine Influenza A (H3N2) Viruses in Europe Journal of Virology, 81 (8), 4315-4322 DOI: 10.1128/JVI.02458-06