Species-specific MARCO-alphavirus interactions dictate chikungunya virus viremia.

Arboviruses are public health threats that cause explosive outbreaks. Major determinants of arbovirus transmission, geographic spread, and pathogenesis are the magnitude and duration of viremia in vertebrate hosts. Previously, we determined that multiple alphaviruses are cleared efficiently from murine circulation by the scavenger receptor MARCO (Macrophage receptor with collagenous structure). Here, we define biochemical features on chikungunya (CHIKV), o'nyong 'nyong (ONNV), and Ross River (RRV) viruses required for MARCO-dependent clearance in vivo. In vitro , MARCO expression promotes binding and internalization of CHIKV, ONNV, and RRV via the scavenger receptor cysteine-rich (SRCR) domain. Furthermore, we observe species-specific effects of the MARCO SRCR domain on CHIKV internalization, where those from known amplification hosts fail to promote CHIKV internalization. Consistent with this observation, CHIKV is inefficiently cleared from the circulation of rhesus macaques in contrast with mice. These findings suggest a role for MARCO in determining whether a vertebrate serves as an amplification or dead-end host following CHIKV infection. [Display omitted] • Specific biochemical features of alphaviruses facilitate MARCO-dependent clearance in mice • Murine MARCO binds and internalizes CHIKV, ONNV, and RRV via the SRCR domain • MARCO SRCR domains from ungulates, but not potential amplification hosts, internalize CHIKV • Unlike mice, rhesus macaques inefficiently clear CHIKV after intravenous inoculation Li et al. find that murine MARCO enhances alphavirus internalization and limits viremia based on specific virion features. Although MARCO from several species promotes CHIKV internalization, MARCO from known or potential CHIKV-amplifying hosts does not, and rhesus macaques failed to clear CHIKV from blood circulation. These findings suggest MARCO impacts CHIKV transmission. [ABSTRACT FROM AUTHOR]