Insertion-in-process provides firsthand look at how retroviruses get incorporated into genomes
By Charles Q. Choi | July 6, 2006
The koala genome is in the middle of an invasion from a retrovirus, presenting a unique opportunity to observe how these viruses incorporate themselves into a wild species, researchers report in this week'sNature.
Retroviruses that have integrated themselves into their host genomes, known as endogenous retroviruses, are widespread among mammals. However, all other endogenous retroviruses embedded themselves into genomes thousands -- if not millions -- of years ago, according to coauthor Paul Young at the University of Queensland in Australia. "By studying how koalas deal with this viral invasion, it will give us clues as to how retroviruses first engaged with our ancestors and those of other species," Young told The Scientist.
Over time, mutations and deletions often inactivate endogenous retroviruses. Scientists previously identified the koala retrovirus (KoRV) as an endogenous retrovirus because it was present in all koalas tested for it during an earlier experiment. However, KoRV is unusual in that it possesses a full-length genome capable of replicating and generating viral particles, and is closely related to an exogenous retrovirus, gibbon ape leukemia virus (GALV), which originated from outside the host.
Additional data suggested that KoRV most closely resembled an exogenous virus. In Southern blotting analyses of DNA from unrelated captive and wild koalas, Young and his colleagues found that KoRV insertions exhibited considerable variation in number and pattern, a finding not seen in most endogenous retroviruses. Sequencing KoRV envelope gene's hypervariable region showed nearly two-thirds of all its mutations were silent -- also unusual for endogenous viruses, where loss of function is expected to happen through random mutations.
To investigate how KoRV might have infiltrated koalas, the researchers conducted polymerase chain reaction (PCR) analyses on DNA extracted from blood samples gathered from the wild koala population. Surprisingly, Young and his colleagues found koalas on Kangaroo Island off the south coast of Australia were apparently not infected with KoRV. The retrovirus was present in some koala populations in southern Australia, but not all, whereas animals further north in Queensland uniformly tested positive. This pattern suggests the virus is transitioning between exogenous and endogenous forms, spreading from northern to southern Australia, according to the researchers.
Hunters largely exterminated koalas from mainland southern Australia during the late 19th and early 20th centuries. The area was restocked from populations established in the early 1900s on Kangaroo Island and other isles that have remained isolated since the 1920s. Since KoRV is largely absent from these island and southern Australian populations, it likely entered the koala genome within only the last 100 years, the authors add.
Previous laboratory research has observed retroviral integration-in-process in mice, but this work shows "a real life situation," noted co-author Rachael Tarlinton via Email.
Future studies can determine what receptor KoRV uses to enter germ line cells. "Is there a homolog of this receptor in placental animals, humans? Because GALV is a primate virus, I suspect there is one," Antoinette van der Kuyl at the University of Amsterdam in the Netherlands, who did not participate in this study, told The Scientist in an Email. "Are there specific mutations in KoRV to adapt the virus to marsupials? Did KoRV also spread to other Australian species?"
Researchers should also pinpoint the common ancestor of KoRV and GALV, and which species transmitted KoRV to koalas in the first place, van der Kuyl added. Maribeth Eiden at the National Institute of Mental Health in Bethesda, also not a co-author, proposed Asian rodents as the source for both KoRV and GALV, having found KoRV-like sequences in several. "We need to entertain the possibility this class of viruses -- gammaretroviruses -- are an emerging infection that's zoonotically spread," Eiden told The Scientist.
Charles Q. Choi
Links within this article
R.E. Tarlinton et al. "Retroviral invasion of the koala genome." Nature, published July 6, 2006.
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JJ Hanger, et al, "The nucleotide sequences of koala (Phascolarctos cinereus) retrovirus: a novel type C endogenous virus related to gibbon ape leukemia virus," Journal of Virology, May 2000.
R. Jaenisch. "Germ line integration and Mendelian transmission of the exogenous Moloney leukemia virus." PNAS, April 1976.
Antoinette van der Kuyl
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