A review of the Article: “Simian TRIM5α proteins reduce replication of herpes simplex virus”
Herpes Simplex Virus (HSV) is a DNA virus and HSV-1 and HSV-2 are two very well studied common serotypes. Both of these serotypes belong to the family Herpesviridae and they can infect a wide range of hosts. HSV is known to be the natural causative agents of numerous human diseases in patients of different age, sex and ethnic groups. (Mahy, B.,2001; Webster and Granoff, 1994). In spite of being a very successful human infectious disease agent HSV failed to cause disease in many non-human primates including Rhesus macaques. The reason of HSV being unable to cause disease in Rhesus macaques was hypothesized to be the presence of tripartite motif 5α (TRIM5α) protein in host-cell cytoplasm and nucleus which negatively affect the life cycle of HSV in the host. (Reszka, N., et al.,2010).
In order to justify the hypothesis a number of tests were performed by the researchers involving several sophisticated techniques. At first, HeLa cells and rhesus monkey fibroblasts were infected with HSV-1 KOS and HSV-2 186 and incubated in optimal condition. It was revealed that both HSV-1 and HSV-2 were growing 100 times better in the HeLa cells in compare to those in rhesus monkey fibroblasts. Followed by that the effect of TRIM5α protein in growth of HSV in normal HeLa cell (H-L) and rhesus TRIM5α protein expressed HeLa cell (H-R) were observed and found that during the early growth stage the TRIM5α protein reduced the growth of HSV but over time that effect become lighter. These results made the researchers curious about the ability of TRIM5α protein from different primates as well as human to inhibit the growth of HSV-2. It was found that human TRIM5α protein was most inefficient to limit the growth of HSV-2 where the rhesus TRIM5α protein was the most efficient. (Reszka, N., et al.,2010).
Western blot analysis was performed to measure the significance of rhesus TRIM5α on protein synthesis of HSV-1 and HSV-2. It was revealed that the reduced growth of HSV-1 and HSV-2 had a corresponding association with IE gene expression. After that, the strain specificity of rhesus TRIM5α on different HSV was tested by using clinical isolates and previously tested strains of HSV. This experiment showed that rhesus TRIM5α was not uniformly effective to inhibit the growth of the HSV. Rhesus TRIM5α was totally defenseless in front of HSV strain 17syn+ which demonstrated the strain-specificity of rhesus TRIM5α (Reszka, N., et al.,2010).
In this stage of study the researchers were concentrated on the capability of rhesus TRIM5α to hold on to the HSV infected cell protein 0 (ICP0) in the cell cytoplasm and they conducted an immunofluorescence study. From the experimental observation it was discovered that rhesus TRIM5α amplify the amounts of ICP0 in the infected cell cytoplasm and that interfere with the nuclear function of the host cell which inhibit the HSV growth in the cell. In order to find the credibility of the study the researchers tested the effect of TRIM5α on HSV-1 ICP0-mutant replication and found that the inhibition of HSV by TRIM5α was not relied on the absence of ICP0. Throughout these experiments the researchers also found a unique characteristic of HSV as this virus can initiate the loss of function of its inhibitory protein TRIM5α which could lead to the gradual loss of function for all the TRIM5α molecules present in the infected host cell. (Reszka, N., et al.,2010).
Reszka, N., Zhou, C., Song, B., Sodroski, J.G., Knipe D. M., 2010. Simian TRIM5α proteins reduce replication of herpes simplex virus. Virology, doi:10.1016/j.virol.2009.11.041
Mahy, B.W., A dictionary of virology.3rd ed. California: Academic Press, 2001. Print.
Webster, R.G., and Granoff, A., Encyclopedia of Virology. Vol. 2.California: AcademicPress, 1994. Print.