The Yamashita Lab studies the molecular and cellular basis of HIV-1 replication. A major research focus in our lab is the viral capsid, a key molecular complex that encloses viral and host molecules essential for infection. Multifaceted roles played by the viral capsid contribute to shaping the unique HIV-1 biology, including the ability to infect non-dividing cells, preferential integration within active genes and innate immune evasion. Studies of our group include a detailed analysis of capsid evolution, capsid-host interactions and mechanisms of capsid-targeting antivirals. Results from these experiments will have broad implications for basic research on HIV-1 biology as well as for therapeutic applications, such as drug development targeting the viral capsid. Another direction of our lab is single-cell analysis of HIV-1 replication. A major goal of this project is to gain quantitative, mechanistic, and biological insights into cell-to-cell variation in HIV-1 transmissibility. Towards this end, we are developing single-cell assays to quantify virus production and transmission by individual virus-infected cells.
The major goal of this project is to elucidate how the HIV-1 capsid coordinates multiple post-entry events to maximize viral fitness. The viral capsid undergoes structural and functional "metamorphosis" to yield pre-integration complexes after completion of reverse transcription. Core disassembly is regulated by both intrinsic capsid stability and capsid binding proteins and influences cytoplasmic and nuclear events, such as reverse transcription, nuclear entry and integration targeting. We employ a broad range of experimental approaches to comprehensively understand viral and cellular determinants for core stability and disassembly and to delineate their functional significance in capsid-mediated intracellular processes, including HIV-1 immune evasion. Results from these experiments will have broad implications for basic research on HIV-1 biology as well as for therapeutic applications, including drug development targeting the viral capsid.
Single-Cell Analysis of HIV-1 Replication
Recent technological advances in single-cell techniques revealed a considerable degree of functional and phenotypic heterogeneity between individual cells. It is unclear how such cell-to-cell variation affects HIV-1 transmission by virus-producing cells. The major goal of this project is to gain quantitative, mechanistic and biological insights into cell-to-cell variation in HIV-1 transmissibility at the single-cell level. Towards this end, we are developing single-cell assays to quantify virus production and transmission by individual virus-infected cells in vitro.