What is special about pandemic HIV-1? How capsid cofactor interactions regulate DNA synthesis, innate immune detection and pandemic potential

The HIV-1 pandemic arose from a single virus that jumped from chimpanzees to humans, but most related monkey viruses cannot spread between people. This project asks what makes that one virus so different. The answer appears to lie in the virus’s capsid—the protein shell that surrounds its genetic material. The capsid is not just a protective container; it acts as a molecular machine that recruits host cell proteins to orchestrate infection while dodging the immune system. The researchers will use structural biology, single-molecule techniques, and chemical biology to map exactly how the capsid interacts with host cofactors, how those interactions control DNA synthesis and genome uncoating, and how they allow the virus to evade innate immune detection. This is fundamental science. It addresses a long-standing gap in understanding why only certain lentiviruses become pandemics. If successful, the work could reveal why HIV-1 is uniquely transmissible among humans and identify new vulnerabilities in the capsid. The team also has a series of novel capsid inhibitors that they will use as research tools—and potentially as the basis for a new class of antiviral drugs. Deeper knowledge of capsid mechanics could eventually inform pandemic preparedness and treatment strategies, though practical applications remain downstream.