Breakthrough Discovery in HIV Research Opens Path to New & Better Therapies–Difference at Single Nucleotide Site Is Basis for Two Structurally Different HIV RNAs in Same Cell; Intracellular Balance Between Two Is Key

New research on the structure of the human immunodeficiency virus (HIV) has revealed a promising novel drug target for treating HIV infection, which affects more than 1 million Americans and 40 million people worldwide. The findings, published in the April 24, 2020 issue of Science, show that the virus's genetic code can be read in two different ways by cells the virus has infected. The result is that infected cells make two different forms of the virus's RNA. The Science article is titled “Structural Basis for Transcriptional Start Site Control of HIV-1 RNA Fate.” "This functional diversity is essential for the virus to replicate in the body. The virus has to have a proper balance between the two forms of RNA," says Joshua Brown, PhD, at the University of Maryland Baltimore County (UMBC), the lead author on the study. "For decades, the scientific community has known that two different structural forms of HIV RNA exist--they just didn't know what controls that balance. We've discovered that a single nucleotide [site] is having a huge effect, which is a paradigm shift in understanding how HIV works." Crucially, "You can imagine that if you could come up with a drug that would target the genetic code at that one specific spot, and shift it to one form only, then it could prevent further infection, theoretically," says Dr. Brown, who earned his PhD from UMBC in 2018 and continues to conduct research there while completing his MD. Science Magazine introduced the article with the following explanation of the new findings: “RNA transcripts of the HIV-1 RNA genome can be either spliced and translated into viral proteins or packaged into new virions as a progeny genome. The path taken depends on whether the transcript contains one guanosine at the 5′ terminus (1G) rather than two or three (2G or 3G). Brown et al.
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