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The Secrets of Antisense Transcripts in HIV-1

Learn how antisense transcripts affect HIV-1's behavior and treatment response.

Adam A. Capoferri, Rachel Sklutuis, Toluleke O. Famuyiwa, Sachi Pathak, Rui Li, Jason W. Rausch, Brian T. Luke, Rebecca Hoh, Steven G. Deeks, John W. Mellors, John M. Coffin, Jennifer L. Groebner, Fabio Romerio, Mary F. Kearney

― 5 min read


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Table of Contents

HIV-1, the virus that causes AIDS, is like a sneaky thief that hides in our bodies and can be tough to track down. One of the clever tricks it uses involves a type of RNA called antisense transcripts (AST). Think of these AST as the virus's secret notes. Instead of just sending out the usual messages to make more virus, these secret notes can also play a role in controlling the game. They can either help or hinder the virus's ability to multiply and stay hidden from the Immune System.

What Are Antisense Transcripts?

Antisense transcripts are RNA molecules that are made from the opposite strand of a gene. In simple terms, if one strand of the DNA is sending out messages to make proteins, the antisense strand is like the sidekick that can provide backup or even throw a wrench in the works. These transcripts have been found in all sorts of living beings, from simple bacteria to complex human cells, and they’re believed to have a variety of functions.

The Role of Antisense Transcripts in HIV-1

In the case of HIV-1, these antisense transcripts have been shown to have important roles. They can participate in managing how the virus behaves at different stages of its life. For instance, they help keep the virus's genes hidden away when the immune system is on the lookout, allowing HIV-1 to remain quiet but still present in the body. This is particularly relevant in people undergoing treatment for HIV, where the virus can remain dormant and undetectable.

Detecting Antisense Transcripts in People with HIV

Scientists have been keen to look at these transcripts in actual people living with HIV. They have studied different groups: some individuals were on Antiretroviral Therapy (ART), which is a treatment to keep the virus in check, while others were not. The goal was to see how these antisense transcripts behaved in different situations.

By collecting blood samples, researchers tried to measure how many of these antisense transcripts were in the blood of those on ART compared to those who were not. What they found was that people on ART tended to have more of these transcripts. It was almost like the virus was having a little party in those cells-just waiting for the chance to come out and play when the treatment wasn’t around.

The Participants and Their Details

The study included a small group of people living with HIV. Most of the participants were assigned male at birth, and they varied in race and ethnicity. The time they had been infected with HIV ranged from a few years to over a decade. Those not on ART had detectable levels of the virus, while most of those on treatment had nearly undetectable levels. This shows how effective ART can be in managing the virus's presence but also highlights the stealthy nature of HIV-1.

How Researchers Collected and Analyzed Samples

To get a clear picture, researchers used specific methods to isolate RNA from the blood cells of the participants. They then compared the levels of antisense transcripts in both groups. Like a good detective, they had to make sure that their findings weren't just due to errors or outside contamination. They used a variety of controls and double-checked their results to ensure what they found was real and meaningful.

Findings: Antisense Transcripts Are Present!

The results showed that antisense transcripts were indeed detected in all participants, whether they were on ART or not. The amounts of these transcripts were notably higher in those receiving treatment. While the number was generally low, just a few copies of antisense transcripts could make a big difference in HIV's ability to hide and persist in the body.

A Closer Look at the Results

In one interesting instance, a participant who had been on ART for several years showed variations in the number of antisense transcripts at different times. This finding suggests that even with consistent treatment, the behavior of the virus and its transcripts could shift, hinting at the complexity of HIV-1’s interaction with treatment.

What's Next for Research?

The researchers concluded that antisense transcripts might play a crucial role in the way HIV-1 persists in the body, particularly in individuals who are on ART. The findings open new pathways for research that could ultimately lead to improved treatments.

Scientists may want to look at whether these antisense transcripts are produced by viral or human genes. The ability to distinguish between the two could help in understanding how to better control the virus and its effects on the human body.

The Importance of Understanding Antisense Transcripts

Understanding antisense transcripts is crucial because they could be key players in controlling HIV-1 without relying solely on antiretroviral therapy. They could reveal new strategies that lead to new treatments or even a cure.

Conclusion

In summary, antisense transcripts in HIV-1 offer interesting insights into the virus's life cycle. They help explain why the virus can be so difficult to eliminate from the body, even with treatment. As research continues, there’s hope that better understanding these “secret notes” of the virus will lead to better tools in the fight against HIV/AIDS.

After all, if there's one thing we’ve learned, it’s that this virus loves to play hide and seek. And who knows? Maybe one day we’ll find the best hiding spots and uncover the secrets of HIV-1 once and for all.

Original Source

Title: In vivo detection of HIV-1 antisense transcripts in untreated and ART-treated individuals

Abstract: Natural antisense transcripts are expressed in eukaryotes, prokaryotes, and viruses and can possess regulatory functions at the transcriptional and/or post-transcriptional levels. In vitro studies have shown that HIV-1 antisense transcripts (AST) promote viral latency through epigenetic silencing of the proviral 5' long terminal repeat (LTR). However, expression of HIV-1 AST in vivo have not been convincingly demonstrated. Here, we used single RNA template amplification, detection, and sequencing to demonstrate expression of AST in unstimulated PBMC collected from people with HIV-1 (PWH). We found that AST had high genetic diversity that matched proviruses in cells from blood and lymph nodes. We measured a median of 26 copies of AST per 100 infected cells in PWH on ART and a median of 2 copies per 100 infected cells in PWH not on ART. The expression of HIV-1 AST in vivo is consistent with a potential regulatory role in regulation of HIV-1 expression.

Authors: Adam A. Capoferri, Rachel Sklutuis, Toluleke O. Famuyiwa, Sachi Pathak, Rui Li, Jason W. Rausch, Brian T. Luke, Rebecca Hoh, Steven G. Deeks, John W. Mellors, John M. Coffin, Jennifer L. Groebner, Fabio Romerio, Mary F. Kearney

Last Update: 2024-12-06 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.12.06.627170

Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.06.627170.full.pdf

Licence: https://creativecommons.org/publicdomain/zero/1.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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