Human genome bears a virus related to HIV-1

November 08, 1999

November 9, 1999 - Buried within the genetic blueprint of every human is a snippet of DNA that resembles a gene sequence from the human immunodeficiency virus (HIV). Humans have been carrying this unwanted genetic baggage around for more than 30 million years, according to researchers from the Howard Hughes Medical Institute (HHMI) at Duke University.

"We're all walking around with a little bit of an HIV-like sequence in our genes," said Bryan Cullen, an HHMI investigator at Duke University.

According to Cullen and his colleagues, an ancient family of viruses, known as HERV-K (for human endogenous retrovirus K), took up permanent residence in the genetic material of Old World monkeys shortly after they diverged from New World monkeys. The viruses then traveled with their simian and pre-human hosts as these species moved along the evolutionary path that led to Homo sapiens. Cullen's group published its findings in the November 9, 1999, issue of the Proceedings of the National Academy of Sciences.

During infection, some viruses insert their DNA into the host's genome and direct the host's cellular machinery to make the proteins needed to assemble more viruses. If this gene insertion takes place in a cell that will become an egg or a sperm, the host's offspring will have a copy of the virus in every single cell. "Once it's in there, it doesn't get out," Cullen said.

Because of these viral gene insertion events, genetic material from inactive viruses accounts for roughly 3 percent of the human genome. Cullen says that 30-50 copies of HERV-K exist in the human genome, and that some of the copies appear to be active at a low level in normal testicular and placental tissue. The HERV-K genes show even more activity in certain cancers, especially those involving the testes, "but there doesn't seem to be a harmful effect from the activity of these genes," Cullen said.

The consistent presence of HERV-Ks, however, offers insight into the evolution of both humans and viruses. First, it offers "very good evidence confirming that humans evolved from monkeys, specifically Old World monkeys." Perhaps more importantly, though, Cullen and his group determined that the HERV-K viral protein, K-Rev, functions in a manner similar to the HIV Rev protein. "This suggests that certain disease-causing tools used by HIV may have been around much longer than we had previously thought," said Cullen.

Rev, a protein which is produced by human T-cell leukemia viruses in addition to HIV, ushers viral messenger RNAs from the nucleus of a host cell into the cytoplasm, where they direct the cell's machinery to make the building blocks for more viruses. Rev accomplishes this transport by controlling a human protein known as Crm1. Without this Rev-Crm1 pair, viral messenger RNA would remain trapped inside the host's nucleus, and the virus would be unable to reproduce.

Until now, scientists had thought this activity was unique to HIV and human T-cell leukemia viruses, but Cullen and colleagues disagree. Though K-Rev appears quite different structurally from HIV's Rev, Cullen and his colleagues have demonstrated that K-Rev also hijacks Crm1 to transport mRNA from a cell's nucleus to its cytoplasm.

"The gene has been sitting in our genome all these millions of years, and it's in perfect working order," Cullen said.

Is HIV, then, descended from a virus that humans have carried for millions of years? "Probably not," Cullen said. "It's much more likely that HERV-K and HIV descended from a common ancestral virus that had Rev-like activity or that the two viruses exchanged genetic material somewhere in their evolutionary history to create Rev activity."

Cullen said that this discovery could have implications for xenografts, the untested practice of transplanting animal organs, such as kidneys, into humans. With any transplant, the recipients receive not only the organ, but also any viruses that may be living in its cells. In the case of animal-to-human transplants, the procedure brings genetic material from two different species into close contact.

"You now give these viruses an opportunity for genetic exchange, an opportunity not too different from what may have created the REV activity in the first place," explained Cullen.

But beyond such implications, Cullen believes there is a more important insight coming out of this work with K-Rev. "If we had a better idea of how viruses evolve, we might develop better strategies for countering the threats of viral infection," Cullen said.

Howard Hughes Medical Institute

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to