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Abstract
Sexual transmission of HIV-1 consists of processes that exert either positive or negative selection pressure on the virus. The sum of these selection pressures lead to the transmission of only one specific HIV-1 strain, termed the transmitted founder virus. Different dendritic cell subsets are abundantly present at mucosal sites and, interestingly, these DC subsets exert opposite pressure on viral selection during sexual transmission. In this review we describe receptors and cellular compartments in DCs that are involved in HIV-1 communication leading to either viral restriction by the host or further dissemination to establish a long-lived reservoir. We discuss the current understanding of host antiretroviral restriction factors against HIV-1 and specifically against the HIV-1 transmitted founder virus. We will also discuss potential clinical implications for exploiting these intrinsic restriction factors in developing novel therapeutic targets. A better understanding of these processes might help in developing strategies against HIV-1 infections by targeting dendritic cells.
Highlights
The number of new HIV-1 infections globally continues to decline
Mucosal langerhans cells (LCs) capture and internalize HIV-1 leading to degradation, thereby preventing HIV-1 dissemination [38, 39], whereas dendritic cell (DC) play a key role in transmitting the virus to target CD4 T cells
These findings underscore the importance of LCs as initial targets for sexual transmission of HIV-1 and understanding these phenotypic properties of transmitted founder (TF) viruses is essential for vaccine design
Summary
The number of new HIV-1 infections globally continues to decline. From a peak of 3.4 million new infection a year in 1996 to 1.8 million in 2017. Mucosal langerhans cells (LCs) capture and internalize HIV-1 leading to degradation, thereby preventing HIV-1 dissemination [38, 39], whereas DCs play a key role in transmitting the virus to target CD4 T cells. DCs facilitate viral transmission to T cells either by HIV-1 fusion and productive infection of the DC, leading to viral transmission to permissive cells or by capture and internalization of HIV-1 into MVBs and transmission independent of DC infection [36, 37, 41] Besides their role in HIV-1 dissemination they are important in triggering an innate immune response upon viral exposure. After internalization the virions can stay infectious for many days and can be transmitted to CD4positive T cells [45] In this way DCs serve as virus reservoirs to mediate trans-infection of CD4-positive T cells, thereby facilitating spread of HIV-1 to the lymph nodes [45, 46]. This implies that activation of LCs by inflammation or genital coinfection alters the protective function of LCs, mediating HIV-1 transmission (Figure 1), which might be associated with lower expression of langerin on activated LCs as langerin has anti-viral properties [39]
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