A new study has found how a small difference in the RNA sequence can allow the viral RNA to be packaged for replication, creating potential targets for future HIV treatments. The study has been published in the ‘Proceedings of the National Academy of Sciences’. The study found that HIV chose its viral RNA genome – the “source code” that is injected into healthy human cells to infect them – based on functions attributable to just two nucleotides. “It’s just this two-nucleotide difference that makes such a dramatic effect,” said Karin Musier-Forsyth, senior author of the study, Ohio Eminent Scholar and a professor of chemistry and biochemistry at The Ohio State University.
If we can prevent it from packaging its own genome, we can prevent it from spreading inside the body, she added.
The study’s authors, who also included researchers from the National Cancer Institute, hoped to answer a long-standing question in HIV biology research: How does the virus know to package its specific viral RNA to be copied in human cells?
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Just like we need a genome encoded by DNA, viruses have their own genomic DNA or RNA – in the case of HIV it’s RNA – and they have to package their genomic RNA and that’s what this whole study is about. It’s an essential step for how we understand the replication of the virus, she said.
RNA is a string of nucleotides, and it is present in some form or another in all living things, including viruses. In HIV, it carried the genetic information that allowed the virus to copy itself inside a host – the human body. HIV RNA comprised about 9,800 nucleotides.
We have lots of types of RNA in our cells as humans, including messenger RNA (mRNA), which is very abundant – and which everyone has heard about now, thanks to COVID-19, Musier-Forsyth said.
“But the viral genome from HIV is made in small amounts, and it is very selectively packaged as genomic RNA, in addition to serving as mRNA to make viral proteins. How does the virus find this genomic RNA to package and not just package any old RNA in our cells,” she added.
Researchers believed if they could find an answer to that question, they might eventually be able to develop drugs that could block the virus from replicating and stop it from infecting healthy human cells.
The researchers examined the structures of two nearly identical HIV RNA strings and found that the virus used a two-nucleotide difference on the very end of the RNA strings to distinguish between genomic RNA and viral mRNA. One, they found, was more efficient at being packaged as a genome than the other due to the conformations, or structures, that it formed.
The findings could have implications for future HIV treatments that target RNA and would be different from current HIV treatments, which primarily target viral proteins. New HIV drugs based on this discovery are likely years away, but Musier-Forsyth said this finding is an important scientific step.
Now that we understand more about the structure of the RNA, we could develop therapeutics, whether they be small molecules or other new nucleic acid therapeutics, that could lock the RNA into a conformation that wouldn’t be packaged. If it can’t package its genome then it can’t replicate, Musier-Forsyth said.
Other Ohio State researchers who contributed to this study included Shuohui Liu and Jonathan P. Kitzrow. This work was supported by the National Institutes of Health.
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(Except for the headline, this story has not been edited by NDTV staff and is published from a syndicated feed.)
NDTV – Dettol have been working towards a clean and healthy India since 2014 via Banega Swachh India initiative, which is helmed by Campaign Ambassador Amitabh Bachchan. The campaign aims to highlight the inter-dependency of humans and the environment, and of humans on one another with the focus on One Health, One Planet, One Future – Leaving No One Behind. It stresses on the need to take care of, and consider, everyone’s health in India – especially vulnerable communities – the LGBTQ population, indigenous people, India’s different tribes, ethnic and linguistic minorities, people with disabilities, migrants, geographically remote populations, gender and sexual minorities. In wake of the current COVID-19 pandemic, the need for WASH (Water, Sanitation and Hygiene) is reaffirmed as handwashing is one of the ways to prevent Coronavirus infection and other diseases. The campaign will continue to raise awareness on the same along with focussing on the importance of nutrition and healthcare for women and children, fight malnutrition, mental wellbeing, self care, science and health, adolescent health & gender awareness. Along with the health of people, the campaign has realised the need to also take care of the health of the eco-system. Our environment is fragile due to human activity, that is not only over-exploiting available resources, but also generating immense pollution as a result of using and extracting those resources. The imbalance has also led to immense biodiversity loss that has caused one of the biggest threats to human survival – climate change. It has now been described as a “code red for humanity.” The campaign will continue to cover issues like air pollution, waste management, plastic ban, manual scavenging and sanitation workers and menstrual hygiene. Banega Swasth India will also be taking forward the dream of Swasth Bharat, the campaign feels that only a Swachh or clean India where toilets are used and open defecation free (ODF) status achieved as part of the Swachh Bharat Abhiyan launched by Prime Minister Narendra Modi in 2014, can eradicate diseases like diahorrea and the country can become a Swasth or healthy India.