High Risk, High Reward: By Selecting Tsg101, A Protein That Sorts The Trash, As Our Personal ESCRT, Both HIV And I Were Able To Bud

Being asked to write this “Reflections”-type article is a special honor offered at the end of one's career and I am grateful for the opportunity to think back over the more than 4-decade span of my career in the field of HIV/AIDS Retrovirology. Although at this point in time there is still no vaccine or curative therapy for HIV/AIDS, this invitation to reminiscence comes in the year of FDA approval of Lenacapavir, the first-in-class anti-HIV agent targeting the viral capsid. This triumph in the field is the culmination of efforts of many, including some in my own laboratory, who were among the first to produce recombinant capsid protein (CAp24) for structural and biochemical studies. A current drawback of this drug is its low genetic barrier to viral resistance. The research finding considered to be our most important contribution to the field of HIV research was framed by the challenge to suppress the emergence of resistant variants, and I describe the paths that drove me to risk exploration of the non-traditional for potential solutions. Finally, I share my views on what I consider to be an important open question for the future: how to achieve greater diversity and inclusion in Science.