Primate lentiviruses are differentially inhibited by interferon-induced transmembrane proteins

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Interferon-induced transmembrane (IFITM) proteins are key host factors that restrict the entry of a broad spectrum of viruses.
• Viral evasion strategies often lead to resistance against IFITM-mediated restriction.

Purpose of the Study:

• To investigate the differential inhibition of HIV and SIV strains by human IFITM proteins.
• To elucidate the mechanism by which IFITM proteins restrict SIV of African green monkeys (SIV(AGM)) entry.
• To explore potential strategies to overcome IFITM-mediated viral restriction.

Main Methods:

• Assessing the inhibition of various HIV and SIV strains by human IFITM proteins.
• Evaluating the effect of human IFITM2 on SIV(AGM) entry.
• Testing the ability of amphotericin B to overcome IFITM-mediated inhibition of SIV(AGM) and influenza A viruses.

Main Results:

• Human IFITM proteins exhibit varying degrees of inhibition against different HIV and SIV strains.
• SIV(AGM) is significantly restricted by human IFITM2, comparable to its native IFITM3.
• Amphotericin B, a cholesterol-binding compound, effectively overcomes human IFITM2-mediated inhibition of SIV(AGM) entry.

Conclusions:

• IFITM proteins employ conserved mechanisms to restrict the entry of both pH-independent primate lentiviruses and pH-dependent influenza A viruses.
• The findings highlight the potential of targeting host-viral interactions for antiviral strategies.