In recent studies of the TRIM5 gene scientists have observed antiretroviral properties. This ability to restrict viruses has sparked significant interest in the international science community as the TRIM5 in some primates is effective against HIV, giving hope to virologists and those working to eradicate HIV (Welkin & Sawyer, 2009).
Already the TRIM5 of a Rhesus monkey (rhTRIM5) has been used to prevent the infection of human cell lines from HIV-1. The genetic structure of the TRIM5 gene in most primates differs to humans, most notably in the ability of some monkeys to restrict HIV-1 preventing the spread of infection (something which humans are unable to achieve). South American Owl monkeys were among the primates with a resistance to HIV-1. This restriction ability was experimented with and it was determined that Owl monkeys possess coding for cyclophilin A (CypA) in the TRIM5 locus. The ability of CypA to bind to the capsid protein of HIV-1 (thereby identifying the virus) combined with the antiviral capabilities of the TRIM5 provides the Owl monkey with a defence mechanism against HIV-1 and other lentiviruses. Research is already underway using the TRIM5 gene in monkeys to enhance the ability of human cells to recognise the HIV-1 virus. So far scientists have been experimenting with altering amino acids in the Human TRIM5 protein in accordance with the structure of the Rhesus protein to increase the recognition of HIV. This small change has had positive results with improved restriction of HIV-1 (Welkin & Sawyer, 2009).
TRIM5 is always competing with viruses for supremacy and as such its evolutionary process is significantly different from other genes. Instead of a long history of purifying selection with rare instances of genetic innovation, the TRIM5 gene has evolved almost entirely by positive selection with variations in the DNA occurring as the result of various evolutionary changes from insertions and deletions to convergence and exon capture (Welkin & Sawyer, 2009).
It is hoped that the study of TRIM5 and its restriction loci will be invaluable in discovery of new antiviral factors, the identification of other gene functions and maybe even the prevention of HIV (Welkin & Sawyer, 2009).
Already the TRIM5 of a Rhesus monkey (rhTRIM5) has been used to prevent the infection of human cell lines from HIV-1. The genetic structure of the TRIM5 gene in most primates differs to humans, most notably in the ability of some monkeys to restrict HIV-1 preventing the spread of infection (something which humans are unable to achieve). South American Owl monkeys were among the primates with a resistance to HIV-1. This restriction ability was experimented with and it was determined that Owl monkeys possess coding for cyclophilin A (CypA) in the TRIM5 locus. The ability of CypA to bind to the capsid protein of HIV-1 (thereby identifying the virus) combined with the antiviral capabilities of the TRIM5 provides the Owl monkey with a defence mechanism against HIV-1 and other lentiviruses. Research is already underway using the TRIM5 gene in monkeys to enhance the ability of human cells to recognise the HIV-1 virus. So far scientists have been experimenting with altering amino acids in the Human TRIM5 protein in accordance with the structure of the Rhesus protein to increase the recognition of HIV. This small change has had positive results with improved restriction of HIV-1 (Welkin & Sawyer, 2009).
TRIM5 is always competing with viruses for supremacy and as such its evolutionary process is significantly different from other genes. Instead of a long history of purifying selection with rare instances of genetic innovation, the TRIM5 gene has evolved almost entirely by positive selection with variations in the DNA occurring as the result of various evolutionary changes from insertions and deletions to convergence and exon capture (Welkin & Sawyer, 2009).
It is hoped that the study of TRIM5 and its restriction loci will be invaluable in discovery of new antiviral factors, the identification of other gene functions and maybe even the prevention of HIV (Welkin & Sawyer, 2009).
REFERENCES
Welkin, J., & Sawyer, S. (2009). Molecular evolution of the antiretroviral TRIM5 gene. Immunogenetics , 163-176.
Welkin, J., & Sawyer, S. (2009). Molecular evolution of the antiretroviral TRIM5 gene. Immunogenetics , 163-176.
