Endogenous retroviruses – Aiding and abetting genomic plasticity

M. V. Eiden

National Institutes of Health,Building49,MSC4483,Bethesda,Maryland 20892



Retroviruses cause disease by infecting cells,injecting their viral single–stranded RNA genome into them and then using their own RNA-directed DNA polymerase to make a double-stranded DNA copy of the viral genome. Integration of this retroviral DNA into the genome of the infected host cell allows the virus to use the host cells DNA-directed RNA polymeraseto make messenger RNA and subsequently viral proteins. Making use of the host cell machinery, viral genomic RNA is packaged and exported from the cell. This process engenders a new generation of virus particles competent to infect neighbouring cells or organisms. Retroviruses that maintain their existence by moving from cell to cell,and organism to organism via serial infection events are called exogenous retroviruses. Occasionally, exogenous retroviruses gain the ability to infect germ cells. If this happens, a profound shift in the history of the retrovirus can occur. If germ line-integrated provirus gains a foothold within the species of the infected individual through vertical transmission to its offspring, an endogenous retrovirus comes into existence. This has happened often within mammalian and proto-mammalian species.Infact,retroviralendogenization is so frequent and ancient an occurence that fragments of viruses,collectively called endogenous retroviruses or ERVs,have been used to distinguish inheritor species from one another as they and their accreted ERVs evolve. ERVs are present in the genomes of birds, reptiles, amphibians,fish and mammals. Over millions of years,
most retroviral genomes and retro-elements residing in their host DNAs have been rendered inactive or suppressed by epigenetic mechanisms or mutations. Thus, an understanding of the initial process of how retroviruses enter their host genomes has not been scientifically feasible. This changed recently and dramatically with the discovery of a pathogenic retrovirus that entered the germ line of koalas within the last 200 years. Endogenizing koala retrovirus (KoRV) has retained its ability to produce infectious virus. KoRV is most closely related to gibbon ape leukemia virus (GALV), which was first identified in the early 1970s as an exogenous retrovirus associated with lymphosarcoma and myeloidleukemia in captive gibbons [4]. The adaptive process by which an infectious, leukemogenic ERV becomes a domesticated form of itself,tolerated as a permanent resident in its host, can now be investigated by comparing changes that distinguish KoRV from its exogenous counterpart, GALV. Changes in KoRV proteins that attenuate its virulence and affect its unique host range properties have already been identified [5, 6]. The outcomes of maintaining infectious ERVs or functional ERV elements are variable, and they profoundly influence the evolution of the host genome. ERVs may play a role in speciation or provide the opportunity for the evolution of a fitter species. Animals such as koalas and mice that harbor intact ERVs serve as virus reservoirs, which promote intraspecies and interspecies transmission of ERVs. Many fully functional ERVs,although not expressed in their hosts, can be activated by a variety of agents or by tissue explantation, with porcine endogenous viruses