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Some retroviruses at some point do without the constant reinfection of their host and prefer to be passed on to new victims directly via the germ cells. Traces of these one-sided integration efforts can still be found in the genome of numerous mammals - in the form of foreign sequences that have long since been inactive because they are crippled. Koalas, however, seem to be the scene of a current conquest.
Why simple when it can be complicated. This motto could certainly apply to the replication of retroviruses: Instead of just exploiting the cellular machinery of their involuntary host, they convert their genetic information, which is available as RNA, into a double-stranded DNA and also smuggle this into the genome of the host cell. Once integrated there, the corresponding genes are then read and translated into the desired proteins. Reversing the normal flow of information from DNA to RNA in the opposite direction earned the viruses the "retro" designation.
Some of these uninvited guests stayed forever. They made it into the germ cells of the infected body and were thus transferred to every cell of the offspring. Eight percent of the human genome consists of such snippets from former subtenants, but no need to worry: over the millennia since they were firmly implanted, they have long since become inoperable as virus protein building instructions. Some, however, play a crucial role in various cancers, among others.
The youngest such permanent viral implantation among mammals is a pig virus, which invaded the genome of its host about 5000 years ago. But this record could now belong to the koalas: As Paul Young from the University of Queensland and his colleagues report, the naturalization campaign seems to be in full swing here.
The koala retrovirus in question was initially described as an endogenous virus because it could be detected in all animals examined in a study. Oddly enough, all of the relevant information for replication was still in the genome that he tracked down – as if it had just moved in and the genome had not yet been affected by mutations or the loss of gene segments. In cell cultures, scientists were even able to produce functional viruses with the genetic material they found. In doing so, they also discovered an astonishingly close relationship to a leukemia virus in gibbons, which until now has only existed as an exogenous pathogen. Similarly, the koala retrovirus causes blood cancer in those infected.
In earlier studies, Young and his colleagues found differences in the number of genome copies introduced between individual koalas. In their current analysis, they compared the number and pattern of viral DNA segments introduced into free-living koalas and captive koalas. And found a surprising variability: only a few spots appeared in several animals, and there was none that was common to all. The length of individual fragments suggests that these are still complete versions, and a closer look at past genetic changes makes it clear that these versions are probably even still functional. All in all, rather typical of an exogenous virus that is still actively replicating and constantly infecting new hosts.
But the scientists also detected the traces of enter in the germ cells - as it should be for an endogenous virus. And when they followed the traces of the subtenant in the germ cells of koala families, they actually showed greater similarities in the installation pattern due to family relationships: young animals revealed themselves as a simple combination product of the parental traits.
So what now? exogenous? endogenous? Sometimes it helps to broaden your perspective, thought Young and his colleagues - and analyzed koala DNA from all over Australia. That actually solved the riddle: While the animals in the north of the continent all carried the virus, the conditions in the south were more mixed - here not every koala was infected by a long shot. And on the Kangaroo Islands off the south coast, tree dwellers even enjoyed a completely koala-retrovirus-free zone. Apparently, the pathogen is spreading from north to south, both exogenously and endogenously, the scientists explain. It's not either-or, but still-yet: The virus is in the middle of the transition from the exogenous to the endogenous variant.
Now, the koalas of the Kangaroo Islands were not brought to their new homes until the beginning of the 20th century, where they had lived in isolation since about 1920. Since they show no traces of the retroviruses, their founding fathers and mothers must have been free of them. And since the furry darlings were almost completely wiped out by hunting in the south of the continent in the late 19th and early 20th centuries, the only conclusion that remains is that the retrovirus only managed to take the first step towards finally implanting itself in the koala genome there in the last hundred years. The last one is ahead of him.
