Stop playing seek-and-hide with latent HIV

November 23, 2016

A group of researchers at the Centre for Genomic Regulation (CRG) and the Pompeu Fabra University (UPF) in Barcelona, Spain, have developed a new technology that sheds light on the HIV infection and offers a first glance at the expression landscape of the HIV in the human genome.

After entering the genome of an infected cell, a fraction of the viruses becomes dormant and hence escapes detection by our immune system. These viruses escape therapy treatment and remain a threat for the patient because, at a later time, they will spontaneously awaken and restart the infection cycle. Many current therapies and available drugs aim to reactivate latent HIV in the hope of clearing the latent virus population. Unfortunately, none of the proposed therapies have proved as yet effective to cure infected patients. Foreign viral DNA is silenced in the human genome by the host chromatin, which is a complex of DNA and proteins wrapping and condensing the DNA to form chromosomes.

Chromatin silencing is mediated by several mechanisms and now a team of researchers led by Guillaume Filion, group leader of the Genome Architecture laboratory at the CRG, have developed a technology aimed at discovering the role of the chromatin silencing in the response of latent HIV to the currently available drugs.

As reported in Nature Structural and Molecular Biology today, they developed a technology called B-HIVE, which allowed them to map the HIV inserts within the human genome as well as to measure their expression levels. "We barcoded a population of viruses with a genetic identifier. With the barcodes, we were able to link an individual virus to its chromosomal location" explains Filion, the leading author of this study. Genetic barcoding works like the barcodes of food products in supermarkets: after all the items are labeled, each individual item can be identified by its specific code. "Also, we were able to measure their expression levels and showed that the response of HIV to reactivation therapies partly depends on the integration site in the human genome. For the first time, it shows the practical relevance of the chromatin context in the fight against HIV", states the researcher.

With the use of this new technology, the researchers were able to show that different HIV reactivation drugs reactivate HIV from different locations within the chromosome. In other words, these drugs are more selective than previously thought. "Having this technique in hand, we can now search for the best drug mix that can reactivate all the latent viruses that up to now were hiding from the antiretroviral drugs in use today and make them susceptible to destruction. Our study suggests to orient future investigations towards the development of drugs with complementary targets" says Heng-Chang Chen, CRG researcher and first author of the study. "This is a big step forward and will definitely boost HIV cure research as well as our understanding of the dormant state of HIV called latency," adds enthusiastically Andreas Meyerhans, an HIV researcher co-authoring this paper and ICREA research professor at the UPF.

The new genome-wide maps of HIV expression address a fundamental question that has so far remained unresolved and it provides insight into a basic principles of gene regulation. Hopes are that it will become a favourable and advantageous resource for data analysts interested in clinical applications. While exciting times seem to lay ahead for the researchers, society as a whole can now hope that this exceptional research will be translated into benefit for the community of HIV-infected individuals.

Center for Genomic Regulation

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