Transmission electron micrograph of HIV-1 virus particles. Credit score: NIAID
A brand new examine led by Western researchers is the primary to establish an element that would affect how briskly the pocket the place human immunodeficiency virus (HIV) hides dormant within cells shrinks when handled.
HIV is tough to remedy, partly as a result of virus’ potential to create a “latent reservoir”—the place it hides dormant within cells, protected from detection.
“When this virus is expressed within infected cells, it can trick the immune system into not knowing it’s there,” stated Jimmy Dikeakos, Schulich Medication & Dentistry professor and the examine’s senior writer.
Nef protein, which is expressed by HIV throughout an infection, shields the virus from immune detection. This protein reduces a molecule on the floor of the cell that acts as a marker to assist the immune system acknowledge it’s contaminated.
The examine, revealed in The Lancet Microbe, discovered the flexibility of Nef protein to scale back the marker molecule, referred to as cell floor MHC-I, is linked to the velocity at which the latent reservoir shrinks throughout long-term antiretroviral remedy (ART) therapy.
“For people infected with the virus with highly active Nef—meaning the Nef protein is really good at depleting MHC-I molecules from the cell surface—the rate at which the latent reservoir decayed was much slower than in individuals with less active Nef,” stated Dikeakos, professor within the division of microbiology and immunology.
The examine was half of a big, collaborative international initiative involving the Dikeakos lab in partnership with professor Jessica Prodger at Western, Andrew Redd on the NIH and Rakai Well being Sciences Program in Uganda. This discovery opens the door to new methods that particularly goal the Nef protein as a manner to assist enhance remedies for HIV.
Discovery expands therapy prospects
“By identifying the correlation, it showed that not only can we use treatments that block Nef to target HIV during active replication, but it can be a useful tool to supplement current treatments and cure efforts,” stated Mitchell Mumby, postdoctoral researcher at Schulich Medication & Dentistry and lead writer.
Presently, ART therapy is unable to fully eradicate the virus from the physique and sufferers should take these medicine on daily basis for his or her total lives.
“If we’re going to propose curative strategies, we need to understand what the virus is doing in individuals under treatment,” stated Dikeakos.
Researchers performed this examine with 14 folks residing with HIV and receiving ARTs in Uganda over a five-year interval the place modifications within the dimension of the latent reservoir had been measured.
Primarily based on the proof displaying extremely energetic Nef slowed the discount within the dimension of the latent reservoir, the researchers are actually specializing in growing Nef inhibitors which might immediately goal the virus quite than the host cell.
“The idea would be to include a potential Nef inhibitor that works well with the current ARTs and other cure approaches currently being explored. The hope is that this approach would result in a targeted reduction in the size of latent reservoirs. It’s not a complete elimination, but we hope by doing this over the long term, people’s prognosis will improve,” stated Mumby.
“It’s really about removing those toxic effects from HIV that we know exist, and by reducing this reservoir in this manner, we can mitigate a lot of those effects that are happening.”
This examine was additionally performed in collaboration with Schulich Medication & Dentistry researchers Greg Dekaban, Artwork Poon, Corby Fink, Cassandra Edgar, Steven Trothen and Roux-Cil Ferreira.
Extra data:
Mitchell J Mumby et al, Affiliation between HIV-1 Nef-mediated MHC-I downregulation and the upkeep of the replication-competent latent viral reservoir in people with virally suppressed HIV-1 in Uganda: an exploratory cohort examine, The Lancet Microbe (2025). DOI: 10.1016/j.lanmic.2024.101018
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HIV’s latent reservoir: New insights into Nef protein supply potential technique to enhance therapy (2025, March 13)
retrieved 13 March 2025
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