The dengue virus non-structural protein 1 (NS1) use the scavenger receptor B1 as cell receptor in human hepatic and mosquito cells

Abstract

15Dengue is the most common virus disease transmitted to humans by 16 mosquitoes. The dengue virus NS1 is a multifunctional protein that form part of 17 replication complexes. In addition, NS1 is also secreted, as a hexamer, to the 18 extracellular milieu. Circulating NS1 has been associated with dengue 19 pathogenesis by several different mechanisms. Cell binding and internalization 20 of soluble NS1 result in the disruption of tight junctions and in down regulation 21 of the innate immune response. In this work, we report that the HDL scavenger 22 receptor B1 (SRB1) in human hepatic cells, and a scavenger receptor B1-like in 23 mosquito C6/36 cells act as cell surface binding receptor for dengue virus NS1. 24 The presence of the SRB1 on the plasma membrane of C6/36 cells, as well as 25 in Huh-7 cells, was demonstrated by confocal microcopy. Internalization of NS1 26 can be efficiently blocked by anti-SRB1 antibodies and previous incubation of 27 the cells with HDL significantly reduces NS1 internalization. In addition, the 28 transient expression of SRB1 in Vero cells, which lack the receptor, renders 29 these cells susceptible to NS1 entry. Direct interaction between soluble NS1 30 and the SRB1 in Huh7 and C6/36 cells was demonstrated in vivo by proximity 31 ligation assays an in vitro by surface plasmon resonance. Finally, data is 32 presented indicating that the SRB1 also act as cell receptor for zika virus NS1. 33 These results demonstrate that dengue virus NS1, a bonna fide lipoprotein, 34 usurps the HDL receptor for cell entry and offers explanations for the altered 35 serum lipoprotein homeostasis observed in dengue patients.36 37 Key words: dengue, dengue virus, zika virus, NS1, scavenger receptor B-1. 38 39 The Flavivirus genus, belonging to the Flaviviridae family, includes a group of 40 vector borne viruses of importance in human public health as dengue virus 41 (DENV), Zika virus (ZIKV), yellow fever virus (YFV), Japanese encephalitis virus 42 (JEV) and West Nile virus (WNV). DENV and ZIKV are transmitted by the same 43 arthropods of the Aedes genus and share a similar geographical distribution 44 (Paixão et al 2018). It is estimated that almost half of the world population, 45 distributed in tropical and subtropical zones, is at risk of contracting these 46 diseases (WHO, 2018). The initial symptoms of both DENV and ZIKV infections 47 manifest as a febrile syndrome. Infections with DENV can evolve to 48 hemorrhagic syndrome accompanied of hypovolemic shock, systemic failure 49 and death, mainly in children. In turn, ZIKV infections when acquired during 50 pregnancy, are associated with the occurrence of microcephaly and other 51 neurological severe injuries in the fetus brain (Rather et al 2017). In adults, 52 ZIKV has been associated with the occurrence of Guillan-Barré syndrome which 53 is highly disabling (Song et al., 2017). DENV and ZIKV virions are spherical 54 particles of about 50nm in diameter. The positive RNA genome is about 11Kb in 55 length encoding for 3 structural (Membra...

The potential role of scavenger receptor B type I (SR‐BI) in SARS‐CoV‐2 infection

“…Besides, SR-BI is also acting as a receptor for entry of the Zika virus. 25 This observation could explain the alteration in lipid and lipoprotein metabolism in dengue patients.…”

“…This verdict proposed that ApoA1 drives flavivirus to interact with SR‐BI and subsequent entry. Besides, SR‐BI is also acting as a receptor for entry of the Zika virus 25 . This observation could explain the alteration in lipid and lipoprotein metabolism in dengue patients.…”

Immune functions of pattern recognition receptors in Lepidoptera

“…Studies have confirmed that mosGCTL-7 in mosquitoes is able to bind to the JEV envelope protein via an N-glycan at N154 in a calcium-dependent manner and promote viral infection through the mosGCTL-7/mosPTP-1 pathway (185). SRB1 in human hepatocytes and an SRB1-like receptor in mosquito cells acts as cell-binding proteins that bind to and facilitate internalization of DENV and Zika virus (ZIKV) NS1, resulting in high permeability of endothelial cells and downregulation of the innate immune response (186). In addition, knocking out GNBP in A. aegypti promotes clearance of DENV-2 (187).…”