Tag Archives: retrovirus

Credit: Pixabay.

Ancient retrovirus may make some people more prone to addiction

Credit: Pixabay.

Credit: Pixabay.

Substance abuse is on the rise in the United States, claiming tens of thousands of lives each year. Despite a burgeoning rehab industry and billions of dollars dedicated to research, the underlying causes of drug dependency are still poorly understood. For instance, we don’t know what makes some people more vulnerable to addiction than others.

An international team of researchers recently published a study that suggests the answer to this question may be buried deep in our genetic fabric. According to the findings, an ancient retrovirus present in a higher proportion among people battling drug addiction may be evidence of a physical cause of addiction.

Our dark genes

Although many retroviruses went extinct hundreds of thousands or millions of years ago, they still live on in our DNA. Retroviruses infect cells and replicate by inserting their DNA into their host cell’s genome. Sometimes that cell can be a germ cell, such as a sperm or egg, so the retroviral DNA is inherited by offspring just like a normal gene. Scientists call these elements human endogenous retroviruses (HERVs).

Scientists estimate that up to eight percent of human DNA is made up of retroviral sequences.

Researchers from several institutions, including Oxford University and the National-Kapodistrian University of Athens, studied people who injected drugs in Greece and Scotland. After a basic genetic screening of the study’s participants, the researchers found that drug users were about three times more likely to have remnants of the HK2 retrovirus within a particular gene in their DNA than people who didn’t use drugs. The virus was identified in 34% of drug users tested in Glasgow, Scotland, compared to 9.5% of the local population, and in 14% of Greek patients, compared to 6% of that country’s population.

The HK2 integration is present in only 5-10% of the population, where it may affect the RASGRF2 gene, which is involved in regulating the brain’s dopamine levels. The neurotransmitter dopamine helps control the brain’s reward and pleasure centers but is also involved in addictive behavior when it’s generated in high amounts as a result of drug use.

Earlier, in 2012, scientists had linked the same gene with binge-drinking. 

“We know of clear biological roles for a small number of human endogenous retroviruses. However, there has never before been strong evidence in support of a role in human biology of an endogenous retrovirus that is unfixed, in other words not shared by all individuals in the population. Our study shows for the first time that rare variants of HK2 can affect a complex human trait. The replication of this finding in the distinct Athens and Glasgow cohorts is particularly important,” Professor Katzourakis, from the University of Oxford, who co-directed the study said in a statement.

Although they haven’t established a causal relationship, the correlation identified in the study is strong. The authors suspect that HK2 may predispose a fraction of the population to addictive behavior.

Previously, studies have found a link between HERVs and autoimmune disorders, along with other harmful effects.

“Most people think these ancient viruses are harmless. From time to time, people have shown overexpression of HK2 in cancer, but it has been difficult to distinguish cause from effect. Back in 2012, following a 20-year controversy regarding their pathogenic roles in humans, we sought to test the high-risk hypothesis that HERVs can be responsible for human disease. Our proposal was supported by the Medical Research Council, and now we have strong proof that HERVs can be pathogenic. For the first time, we are able to make a distinction between cause and effect in HERV pathogenicity,” Dr Magiorkinis, from the University of Athens, who led the study added.

The new results may represent evidence for a physical cause of addiction. If that is indeed the case, then the way drug addiction is handled both in medical practice but also in society, where it is highly stigmatized, could be severely disrupted.

Whether discussing heroin, prescription drugs, marijuana, or synthetics, American drug abuse has reached alarming levels. In 2014, the National Institute on Drug Abuse (NIDA) reported that an estimated 24.6 million Americans over the age of 12 had used an illicit drug during the last month. This accounted for 9.4% of the demographic, which is an increase from 8.3% in 2002.

Many drug users are unable to get help because of the stigma attached to their addiction. A link between a genetic trait and addiction might lead to a revolution in the way drug addiction is viewed by the public. 

The next step is to find an actual mechanism by which HK2 manipulates the dopamine system in the brain. Understanding the inner workings of this potential molecular mechanism could also allow scientists to develop better treatments for drug dependence.

“Looking into this “dark” part of the genome will unlock more genomic secrets,” said Dr. Magiorkinis.

Scientific reference: Timokratis Karamitros, Tara Hurst, Emanuele Marchi, Eirini Karamichali, Urania Georgopoulou, Andreas Mentis, Joey Riepsaame, Audrey Lin, Dimitrios Paraskevis, Angelos Hatzakis, John McLauchlan, Aris Katzourakis, Gkikas Magiorkinis. Human Endogenous Retrovirus-K HML-2 integration within RASGRF2 is associated with intravenous drug abuse and modulates transcription in a cell-line modelProceedings of the National Academy of Sciences, 2018; 201811940.

 

Valuable Viruses – ancient infections essential to human development

Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. (Credit: Mike Jones for Wikipedia)

Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. (Credit: Mike Jones for Wikipedia)

We may owe much of what we are as humans to the actions of old viruses. According to a new study from the Stanford University School of Medicine, human cellular development appears to depend on the actions of genetic material left over from ancient viral infections.

The researchers have identified several noncoding RNA molecules that enable a fertilized human egg to become all of the different cell types in the body. All of these molecules have viral origins and all are essential to growth; blocking their action stops cell development.

 

Viral remnants

Many cells, including fertilized eggs, are pluripotent. That is, they can develop into any cell or tissue type in the body. Scientists can even induce fully-developed human cells to become pluripotent by exposing them to the kinds of proteins found in early human embryos, although the molecular details of this process are not well understood.

The Stanford team was interested in how pluripotency begins. Their work extends previous Stanford research showing that early human embryos contain what appear to be significant amounts of viral particles in the cells from ancient genetic material.

“We’re starting to accumulate evidence that these viral sequences, which originally may have threatened the survival of our species, were co-opted by our genomes for their own benefit,” said Vittorio Sebastiano, PhD, assistant professor of obstetrics and gynecology.

Their study focused on long-intergenic noncoding RNA molecules. Among other biological processes, lincRNAs are known to be involved in enabling cells to acquire pluripotency. Although they’re made from DNA, noncoding molecules don’t make proteins directly but influence the protein expression of other genes.

The team employed RNA sequencing to identify which lincRNAs were most expressed in human embryonic stem cells. Most of these molecules contain highly similar and repetitive regions, however, which make them difficult to sequence accurately. The new study was aided by recently-developed and improved sequencing techniques.

The Stanford researchers identified more than 2,000 previously unknown RNA sequences, and found that 146 were specifically expressed in embryonic stem cells. They then focused on the 23 most highly expressed sequences (HPAT1-23) and found that 13 of these were made up almost entirely of genetic material left behind after an ancient infection by the HER-V retrovirus.

A retrovirus spreads by inserting its genetic material into the genome of an infected cell. The cell generates more viral proteins as part of its normal production processes which can then be assembled into a new viral particle that infects other cells.

If the infected cell is a sperm or an egg, these retroviral sequences can be passed to future generations. Our genomes are littered, therefore, with sequences of age-old retroviral infections. Over time, however, evolutionary changes and mutations have depleted their capacity to produce functional proteins and these sequences are considered to be relatively inert.

Blastocyst - day 5. (Credit: Ekem at English Wikipedia. Transferred from en.wikipedia to Commons.)

Blastocyst – day 5. (Credit: Ekem at English Wikipedia. Transferred from en.wikipedia to Commons.)

The team examined the expression of HPAT 1-23 sequences in the human blastocyst – the hollow cluster of cells that grow from the fertilized egg. They found that HPAT2, HPAT3 and HPAT5 were expressed only in the inner cell mass of the blastocyst, the part that becomes the developing fetus. They found that blocking this expression in one cell of a two-celled embryo stopped the affected cell from contributing to that inner mass. Subsequent work also showed that these three genes are also required for changing adult cells into pluripotent stem cells.

 

Only in primates

“This is the first time that these virally derived RNA molecules have been shown to be directly involved with and necessary for vital steps of human development,” said Sebastiano. “What’s really interesting is that these sequences are found only in primates, raising the possibility that their function may have contributed to unique characteristics that distinguish humans from other animals.”

“Previously retroviral elements were considered to be a class that all functioned in basically the same way,” added Jens Durruthy-Durruthy, PhD and postdoctoral scholar. “Now we’re learning that they function as individual elements with very specific and important roles in our cells. It’s fascinating to imagine how, during the course of evolution, primates began to recycle these viral leftovers into something that’s beneficial and necessary to our development.”

So viral material isn’t just tolerated in our cells – it’s vital to how we become people.

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Lead authors for the research paper, published online this month in Nature Genetics, were Sebastiano, Durruthy-Durruthy, and Renee Reijo Pera, PhD, former professor of obstetrics and gynecology at Stanford and now on the faculty at Montana State University. Other Stanford authors were postdoctoral scholars Mark Wossidlo, PhD, Jonathan Davila, PhD, and Moritz Mall, PhD; research associate Diana Cepeda, PhD; former postdoctoral scholar Jun Cui, PhD; graduate student Edward Grow; Wing Wong, PhD, professor of statistics and health research; and Joanna Wysocka, PhD, professor of chemical and systems biology and of developmental biology.
Source: Ancient viral molecules essential for human development, Stanford researchers say

 

First documented case of child cured of HIV

In what may very well become a historic day, Dr. Deborah Persaud of Johns Hopkins University described the first documented case of a child cured of HIV.

hiv

Dr. Persaud, an amfAR grantee, detailed the case of a two-year-old child in Mississippi diagnosed with HIV at birth; the child was immediately put on antiretroviral therapy for 18 months. However, after this period, both the child and his mother stopped showing up and the kid was taken off the therapy for five months. After these five months, when the child was checked in again, doctors were surprised to find no sign of HIV whatsoever; after the initial results were in, they unleashed the swarm of tests, all of which confirmed that he is indeed HIV-free.

“The child’s pediatrician in Mississippi [Dr. Hannah Gay, a pediatric HIV specialist at the University of Mississippi] was aware of the work we were doing, and quickly notified our team as soon as this young patient’s case came to her attention,” said Dr. Rowena Johnston, amfAR vice president and director of research. “Because the collaboratory was already in place, the researchers were able to mobilize immediately and perform the tests necessary to determine if this was in fact a case of a child being cured.”

So how can this be? Just before he checked out of therapy, he was still HIV positive, so what cured him? Was it the therapy he received, that worked even with such a big pause, or did something else happen between 18 and 23 months that cured him? It is still not clear, and this is what must be done now – figuring out the exact mechanism which pushed out HIV out of his system.

“Given that this cure appears to have been achieved by antiretroviral therapy alone,” said Dr. Johnston, “it is also imperative that we learn more about a newborn’s immune system, how it differs from an adult’s, and what factors made it possible for the child to be cured.”

The only other recorded case cured from HIV is a much more complicated one. Timothy Brown, the so-called “Berlin patient” suffered from both HIV and leukemia. His doctor managed to treat his leukemia with a stem-cell transplant from a person who was born with a genetic mutation causing immunity to HIV infection. The result was that he was cured from both diseases. However, while in the case of Timothy Browh, the curing came as a result of complicated, dangerous and expensive results mixed with a great amount of fortitude, this new case is the result of inexpensive, relatively common treatment.

Typically, newborns with infected mothers are put on a preventative treatment in the first several hours of birth to try to prevent the virus from taking hold. If that prophylaxis fails, they are then switched to a three-drug treatment regimen. The Mississippi baby was born in a rural hospital, and it was impossible for doctors to submit him to the preventive treatment, which makes this case all the more interesting. The child, now two-and-a-half years old, is still HIV free; hopefully, his case will be the breakthrough researchers have been waiting for so long.

Koalas in peril of extinction, due to habitat loss and an AIDS-like virus

The koala population has been going down for quite some while now, mostly due to habitat loss and the lack of laws to protect them, but now it seems they have a really, REALLY big problem. It’s recently been reported that koalas from the Queensland area (and not only) are dying from the spread of an AIDS-like virus, and if things keep going this way, they could be extinct in less than 15 years.

Koala Baby07RAM

”We’re seeing a 100 per cent infection rate in the populations we’re studying. On those figures, it should be considered a disease epidemic,” Australian Wildlife Hospital research director Jon Hanger said.

The big problem is that this retrovirus combines with the habitat loss and there already have been reported some local koala extinctions.

“‘We are losing the battle, and koala populations in smaller fragmented habitats are doomed to extinction. ‘We have hammered our biodiversity like you wouldn’t believe. If you look at a map of Australia on Google Earth you’ll see how few fragments of native vegetation are left across the continent. We have gone way beyond the tipping point for many of our ecosystems.”

Having looked at Google Earth I can say that this statement is not an exaggeration by any standards. He also pointed a finger at the “antiquated legislation” which is currently unable to provide any kind of protection to the little furry fellows.

koala-2

”They were written at a time when the main aim was to make it illegal to kill or collect koalas. They need to be urgently revised to factor in threats posed by climate change, the rapid spread of disease and urban development.”

It’s obvious that the needs and expectancies from the legislators have greatly increased, and hopefully they will see this and make the necessary steps. The Australian Wildlife Hospital and University of Queensland have published a progress report on the moving of young koala populations. The greatest distance traveled was 14km and the reproductive success was really high, but the relocated koalas have numerous problems to cope with. Feral dogs, competition for mates, clearing forests and droughts are just a part of what they will have to face.

As it turns out, the risk of extinction has been greatly misscalculated, underestimated by ~ 100 times ! This also raises more questions as 1 in 4 mammals, 1 in 3 amphibians and 1 in 10 birds are threatened with extinction; what happened if the mathematical model has been wrong here too??