Tuesday, January 24, 2012

Gosh!!! We are born because of Retrovirus

I have been told that am writing only on resistance and antibiotics. So this time, for a change am writing on HERV (Human Endogenous retrovirus). Believe me when I say this we all got at least an 8% of our genome filled with retroviral gene as part of evolution. Alas!!! That’s incredibly huge amount.

All humans carry a sequence of human endogenous retrovirus (HERV) as an integral part of their genomes. They are remnants of ancestral infections by retroviruses that have infected the germ-line cells and retained in the gene pool via Mendelian mode of inheritance. The integrated viral DNA is characterized by long terminal repeats (LTR) flanking gag, pro, pol, and env genes. The HERV’s are implicated in human evolution, certain autoimmune diseases, cancers, in pregnancy formation of the placental syncytium and many other roles. The human genome project found several thousand ERVs which were classified into more than 24 families. 

The discovery of ERV took place in the late 1960s and early 1970s. Three types of ERV were found around the same time: avian leukosis virus in the domestic fowl (Gallus gallus), murine leukemia virus and murine mammary tumor virus in the laboratory mouse (Mus musculus). Initially, ERV were discovered by combining virological and immunological methods with Mendelian genetics. Their existence was then confirmed by nucleic acid hybridization.

Fig 1: The location of ERV-V loci on chromosome 19 in five primate species. The ENVV genes are shown in light blue whereas similarity to other HERV proteins are coded as gag (red), pol (green) and env (blue). Taken from Anders etal, BMC publication (Further reading-1)

The ERV’s are grouped into 3 groups- I, II and III on the basis of sequence similarities with each type. Each type is sub classified into many subtypes based on specificity of tRNA primer binding site. Class I are related to Gammaretroviruses, Class II with Betaretroviruses and Class III with Spumaretroviruses. The Class I and III are found in primates, while class II is found to be active recently. A few of class II subgroup HERV-K have been found to be human specific. An interesting property of the majority of the ERV is that they don’t readily re infect the cells from which they are derived, but can infect other species in vitro and invivo. The feature is known as xenotropism.

The possibility of HERV as etiology of disease is manifold. For instance, HERV-W or more commonly known as MS- associated retrovirus (MSRV) is found to be linked with Multiple Sclerosis. (Now that’s just a research hypothesis. No definitive proof as far as I know). Research has also pointed that the HERV is possibly related to HELLP syndrome, Preeclampsia, Schizophrenia etc. 

If that makes you believe that HERV is just engineered into us to cause problems, there is an alternative angle of look into HERV. It is their beneficial roles in humans. The molecular biologists are now more aware of the importance of physiological roles of the ERV in the cell. The most important among them include coding of proteins in reproductive tissues and embryo. Aha, so we humans are born because virus makes things for us to be born. Infact the placental membrane is designed by the viral protein. The “Telomerase” which is important for the viability of stem cell is a retroviral enzyme.

In brief, the HERV’s integrated into the genome pool of various species and remained latent, and a few of them encoded important proteins to the host. The potential damaging sequences then underwent silencing and remained as fossil remnants. Their study helps in construction of a possible phylogenetic tree and serves as a molecular clock. The potential for a more exhaustive research is high, which will guide us in stripping the hidden details of evolution and the mysteries of many diseases.

Further Reading:

Anders L Kjeldbjerg, Palle Villesen, Lars Aagaard and Finn Skou Pedersen. Gene conversion and purifying selection of a placenta-specific ERV-V envelope gene during simian evolution. BMC Evolutionary Biology 2008, 8:266. doi: 10.1186/1471-2148-8-266. 

Mangeney M, Renard M, Schlecht-Louf G, Bouallaga I, Heidmann O, Letzelter C, Richaud A, Ducos B, Heidmann T: Placental syncytins: genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins. Proc Natl Acad Sci USA 2007, 104:20534-20539. 

Antoinette C van der Kuyl, HIV infection and HERV expression: a review. Retrovirology 2012, 9:6. doi:10.1186/1742-4690-9-6

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