Targeting human proteins: a new insight into HIV treatment

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A new treatment approach that targets human proteins – as opposed to the virus – could potentially provide new insight to treat acute HIV-infected patients. Researchers from the University of Southern California (CA, USA) have recently discovered a protein variant in humans that can be targeted to restrict HIV from harming HIV-positive individuals. This immune protein is referred to as Δ20 IFITM2, as it lacks 20 amino acids on its N terminus. Δ20 IFITM2 suppresses the most damaging HIV strains by preventing the virus from infecting cells.

Corresponding author of the study, I-Chueh Huang (University of Southern California), explained: “Most HIV drugs target the virus, but the virus is not stable; it always mutates – problematic because the virus can become resistant to effective drugs.”

Huang and colleagues focused on HIV-1, which is the most widespread type of the virus worldwide. This virus can be classified into two groups depending on the chemokine receptor utilized upon entry: R5 and X4. R5 viruses interact with the CCR5 receptor and are associated with primary infection, whereas X4 viruses bind to the CXCR4 receptor and are associated with later stages of HIV disease.

Within the study the researchers investigated how Δ20 IFITM2 differentially influences R5 and X4 strains, by observing the rate of viral replication in the presence and absence of Δ20 IFITM2. They distinguished that Δ20 IFITM2 differentially restricts X4 and R5, indicating a gatekeeping role of the protein variant.

The researchers also revealed that in the presence of Δ20 IFITM2 in X4 strains, replication was inhibited and that this lack of replication observed was due to the absence of viral entry into the cell. Conversely, Δ20 IFITM2 was displayed to have no effect on the rate of replication of R5.

This difference observed between X4 and R5 HIV-1 could be due to the different cytokine receptor expressions detected at later stages of infection. Consequently, these expression profiles may alter the expression of Δ20 IFITM2; however, the researchers stated that: “Subsequent studies are needed to clarify these issues.”

Regarding the application of this study, Huang cautioned that: “Our findings will not help develop a vaccine because the focus is on innate immunity rather than the virus.”

“Perhaps one day scientists will create medicine that, like ‘HIV cocktails’, have to be taken indefinitely. But the new treatment may be more effective because it is harder for viruses to escape the body’s defenses,” he said.

Sources: Wan-Lin W, Christopher RG, Ming-Ting T et al. Δ20 IFITM2 differentially restricts X4 and R5 HIV-1. Proc. Natl Acad. Sci. USA 114(27), 7112 (2017); www.sciencedaily.com/releases/2017/08/170823184352.htm

 

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