Most viruses you probably know of our transmitted person to person (or from another biological source) in a process called horizontal transmission. However, another transmission pathway exists: vertical transmission. Retroviruses are one example of a virus that can be vertically transmitted.

Retroviruses, as the name implies, work backwards. The traditional pattern of genetic expression is to proceed from DNA, through RNA, and finally into proteins. Retroviruses on the other hand start with their own viral RNA, convert it into DNA, and insert that information into the genome of their host cell. The most familiar retrovirus in modern times is the HIV virus. Occasionally a retrovirus will infect an animal’s germ line, those cells that lead to sperm and eggs. If those reproductive cells are used in fertilization, then the viral DNA becomes a part of the genome of the next generation: it is vertically transmitted.

Retroviral DNA in the genome is referred to as a provirus, and it accounts for four to ten percent of vertebrate genomes (eight percent in humans). According to Jack Lenz, a professor at Albert Einstein College of Medicine, the original functions of proviruses in the human genome are open to speculation. While HIV is harmful to the host, other retroviruses can have positive effects or simply be replicating selfishly but neutrally. While the proviral DNA in the modern human genome is typically categorized under “junk DNA,” Lenz says some sections appear to reactivate every ten to 100 thousand years, reinserting a new copy of themselves into the host DNA. These copies can serve as “genetic fossils” for mapping our evolutionary past.

Jonathan P. Stoye, Head of the Division of Virology at the Medical Research Council’s National Institute for Medical Research in London, authored an article published this June in Nature Reviews Microbiology laying out an overview of the complex relationship between retroviral and vertebrate DNA. Stoye describes an evolutionary arms race on a genetic scale between the regulatory structures in vertebrate DNA and the nimble efforts of the retroviral RNA to reverse transcribe itself. The same genetic fossils studied by Lenz are found in other vertebrate genomes, detailing a history of viral/host interactions dating back many millions of years.

Some retroviruses can be transmitted vertically and horizontally. The subject of several papers since 2006, the koala retrovirus has been devastating zoo and wild populations of the marsupial. The origins of the retrovirus remain unknown; while it resembles a virus found in gibbons, it is unclear how the pathogen might have jumped species. In koalas the virus can produce cancers and an AIDS-like immune disorder.

A paper published this July in the Australian Veterinary Journal, took blood and tissue samples from 708 koalas across the continent. The areas with the highest percentage of pro-virus positive koalas were four regions of Queensland and New South Wales at 100% and mainland Victoria at 72.2%. This suggests a northern location for ground zero of the virus. However the numbers of viral copies per cell differ between these northern regions, from a mean of 165 copies per cell in Queensland koalas to far below one copy per cell in Victorian koalas. According to the authors, this confirms that we are seeing a virus that is transitioning from a horizontal to a vertical means of transmission.

 

Provirus in humans are called junk DNA, but active retroviruses on their way to becoming proviruses can have devastating effects. The retrovirus plaguing koalas today is still poorly understood and HIV in humans, while treatable, still has no cure. In his paper Stoye describes what we might learn by better understanding human proviruses. We know human cells have found ways to neutralize or perhaps even utilize the viral DNA in their genome. If these cellular and genetic defenses can be harnessed, it may lead to a treatment for active retroviruses like HIV or koala retrovirus.

 

 

Sources:

Phone interview with Jack Lenz 10/12/12

Simmons et al. “Prevalence of koala retrovirus in geographically diverse populations in Australia.” Australian Veterinary Journal. Volume 90, Issue 10

Stoye. “Studies of endogenous retroviruses reveal a continuing evolutionary saga.” Nature Reviews Microbiology. 10, 395-406 (June 2012) doi:10.1038/nrmicro2783

 

 

 

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