Single-Cell Technologies Applied to HIV-1 Research: Reaching Maturity

The need for definitive answers probably explains our natural tendency to seek simplicity. The reductionist “bulk” approach, in which a mean behavior is attributed to a heterogeneous cell population, fulfills this need by considerably helping the conceptualization of complex biological processes. However, the limits of this methodology are becoming increasingly clear as models seek to explain biological events occurring in vivo, where heterogeneity is the rule. Research in the HIV-1 field is no exception: the challenges encountered in the development of preventive and curative anti-HIV-1 strategies may well originate in part from inadequate assumptions built on bulk technologies, highlighting the need for new perspectives. The emergence of diverse single-cell technologies set the stage for potential breakthrough discoveries, as heterogeneous processes can now be investigated with an unprecedented depth in topics as diverse as HIV-1 tropism, dynamics of the replication cycle, latency, viral reservoirs and immune control. In this review, we summarize recent advances in the HIV-1 field made possible by single-cell technologies, and contextualize their importance.