Genomics, molecular biology, genetics and biochemistry of HIV-1 infection
HIV-1 is the causative agent of the worldwide AIDS epidemic, affecting greater than 30 million people worldwide. Although the underlying HIV-1 infection can be effectively suppressed with current anti-retroviral regimens, no magic bullet exists to cure infected individuals with the mutability of HIV remaining a constant problem. To this end, I study host factors that interact with the HIV-1 capsid protein CA.
The HIV-1 capsid composed of the single viral protein CA is more than a shell that protects the viral genomic payload from immune sensing and the environment. CA functions to escort the viral genome to the nucleus thereafter facilitating nuclear entry (Yamashita et al. Journal of Virology. 2004.) and viral integration site preferences (Sowd et al. PNAS. 2016.). Further, CA mutations that alter capsid stability have severe consequences for HIV-1 infection (Forshey et al. Journal of Virology. 2002.), and CA is the most genetically fragile region of the viral genome (Rihn et al. PLoS Pathogens. 2013.) underscoring the importance of the protein to productive infection. Thus, CA is a prime target for HIV-1 anti-retrovirals (Shi et al. Journal of Virology 2011.). With this in mind, we study host proteins and metabolites that modulate HIV-1 CA function during viral entry, integration, and maturation using diverse techniques including deep sequencing, biochemical characterization of HIV-1 virions/capsids, and gene knockout studies of host factors.