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Emaciated cow dying of trypanosomiasis

APOL1 protects humans and primates against trypanosomiasis

Cattle are susceptible to infection with all three major species of African Trypanosomiasis:- Trypanosoma brucei, T. vivax and T. congolense . In contrast humans are only susceptible to two subspecies of T. brucei: T. b. rhodesiense and T. b. gambiense. The human infectious parasites also infect cattle but rarely cause them to develop the disease. Human resistance to T. b. brucei, T. congolense and T. vivax is mediated by the APOL1 protein, which is lethal to these parasites and is both necessary and sufficient to protect humans from these infections [1]. APOL1 is only found in humans and some primates. Humans are susceptible to T. b. rhodesiense because the parasites have developed a protein of their own called SRA that inhibits the APOL1 protein. The APOL1 gene varies amongst primates and the baboon version of the gene provides complete protection against all species of African trypanosomes including the human infective ones.

Zebu Boran bull susceptible to trypanosomiasis

Mice can also be protected by APOL1

It is possible to protect mice against infection with African trypanosomes by injecting them with a copy of the APOL1 gene [2, 3]. The human gene protects mice against cattle parasites but the baboon gene protects against both cattle and human parasites. It is important to protect cattle against the human parasites because cattle are a reservoir of parasites that infect humans, particularly in East Africa. Cattle that are resistant to just cattle parasites could potentially cause an increase in human infections since farmers would no longer have any reason to treat the animals. Conversely cattle that are resistant to both types of parasites could reduce the prevalence of human sleeping sickness in East Africa by removing an important reservoir of parasites that are kept close to human homes. In West Africa this would be less important because humans and not cattle are the main reservoir of sleeping sickness in this area.

Ndama cow tolerant of trypanosomiasis

Creating cattle with the APOL1 gene

A consortium of scientists from New York University, ILRI, the Roslin Institute and The University of Liverpool have been awarded a grant by The National Science Foundation of the USA and the Bill and Melinda Gates Foundation under the BREAD scheme to develop a small number of cattle carrying the APOL1 gene. This project poses significant technical challenges to reproducibly introduce a gene into a specific place in the cow genome (the ROSA26 locus) without permanently adding antibiotic resistance genes as well. We expect that the first cattle carrying the APOL1 gene will be born in 2013. We will then be able to undertake tests to show whether the gene provides the expected resistance to trypanosomiasis in cattle and also that it does not cause any adverse effects on the cattle.

This story of the discovery of the APOL1 gene and how it could be used for treating humans and cattle has been described in this paper in Nature Medicine. A review of the state of livestock transgenics was published in The Scientist in June 2014.

  1. Pays E, Vanhollebeke B: Mutual self-defence: the trypanolytic factor story. Microbes Infect 2008, 10(9):985-989.
  2. Thomson R, Molina-Portela P, Mott H, Carrington M, Raper J: Hydrodynamic gene delivery of baboon trypanosome lytic factor eliminates both animal and human-infective African trypanosomes. Proc Natl Acad Sci USA 2009, 106(46):19509-19514.
  3. Molina-Portela MP, Samanovic M, Raper J: Distinct roles of apolipoprotein components within the trypanosome lytic factor complex revealed in a novel transgenic mouse model. Journal of Experimental Medicine 2008, 205(8):1721-1728.