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Abstract
Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s) that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM) and TYRO3, AXL and MER (TAM). Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.
Highlights
Within the Flaviviridae family, the genus, Flavivirus, encompasses more than 70 enveloped viruses, many of which are transmitted to vertebrates by the bite of hematophagous arthropods, such as Viruses 2014, 6 mosquitoes and ticks
We recently provided new insights into the cell biology of flavivirus infection and identified an unexpected role of PtdSer and the T-cell immunoglobulin and mucin domain (TIM) and TAM proteins in the flavivirus entry program
This study suggests that, by mimicking apoptotic cells, flaviviruses manipulate the physiological functions of the TIM and TAM molecules for infection and probably to broaden their tropism
Summary
Within the Flaviviridae family, the genus, Flavivirus, encompasses more than 70 enveloped viruses, many of which are transmitted to vertebrates by the bite of hematophagous arthropods, such as Viruses 2014, 6 mosquitoes and ticks. The entry of flaviviruses into their target cells is mediated by the interaction of the E glycoprotein with cell surface receptors. Recent studies proved that a lineage I WNV strain was capable of infecting and replicating in cells lacking αvß integrin [11]. These findings do not eliminate a role for αvß integrin during the virus infection process, but they do suggest that αvß integrin is not absolutely required for entry in every cellular context. The best-characterized protein families that bind to and enhance flavivirus infection are C-type (calcium-dependent) lectin receptors and the recently identified phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM) and TYRO3, AXL and MER (TAM), which will be discussed in detail
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