Force‐induced globule–coil transition in laminin binding protein and its role for viral–cell membrane fusion

Abstract

The specific interactions of the pairs laminin binding protein (LBP)-purified tick-borne encephalitis viral surface protein E and certain recombinant fragments of this protein, as well as West Nile viral surface protein E and certain recombinant fragments of that protein, are studied by combined methods of single-molecule dynamic force spectroscopy (SMDFS), enzyme immunoassay and optical surface waves-based biosensor measurements. The experiments were performed at neutral pH (7.4) and acid pH (5.3) conditions. The data obtained confirm the role of LBP as a cell receptor for two typical viral species of the Flavivirus genus. A comparison of these data with similar data obtained for another cell receptor of this family, namely human αVβ3 integrin, reveals that both these receptors are very important. Studying the specific interaction between the cell receptors in question and specially prepared monoclonal antibodies against them, we could show that both interaction sites involved in the process of virus-cell interaction remain intact at pH 5.3. At the same time, for these acid conditions characteristic for an endosome during flavivirus-cell membrane fusion, SMDFS data reveal the existence of a force-induced (effective already for forces as small as 30-70 pN) sharp globule-coil transition for LBP and LBP-fragments of protein E complexes. We argue that this conformational transformation, being an analog of abrupt first-order phase transition and having similarity with the famous Rayleigh hydrodynamic instability, might be indispensable for the flavivirus-cell membrane fusion process.

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population

“…It was found that it was proteolysis of extracellular matrix proteins with serine protease from mosquito saliva that increased viral attachment to heparan sulfate proteoglycans, thereby augmenting dengue virus infectivity in vitro [119] . In addition, three proteins from the ECM proteoglycans pathway (integrin subunit beta encoded by ITGB3, laminin subunits beta 1 and beta 2 encoded by LAMB1 and LAMB2) can interact physically with the whole TBEV particle or with its proteins [69, 72, 120].…”

Tick-Borne Encephalitis Virus: A Structural View

“…The entry process of flaviviruses occurs mainly via receptor-mediated endocytosis, but entry via micropinocytosis is also possible [ 58 , 59 , 60 ]. There are two major receptor candidates for TBEV in mammalian cells, laminin-binding protein (LBP) and the αVβ3 integrin but no receptor candidates in tick cells have been identified so far [ 61 , 62 , 63 ]. Studies using anti-idiotypic antibodies suggested that there could be other receptor candidates of as yet unknown identity [ 61 , 64 , 65 ].…”

Valosin-containing protein (VCP/p97) plays a role in the replication of West Nile virus

“…WNV attaches to host cells through the interaction of the viral E protein and cellular receptors on the surface of host cells (Fields et al, 2013). Several attachment receptors of WNV have been reported and include the laminin receptor (Bogachek et al, 2010;Perera-Lecoin et al, 2014;Zaitsev et al, 2014;Zidane et al, 2013), TIM (T cell/transmembrane, immunoglobulin and mucin) and TAM (Tyro3, Axl and Mer) families (Carnec et al, 2016;Morizono and Chen, 2014;Perera-Lecoin et al, 2014), DC-SIGN/L-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) (Davis et al, 2006;Denizot et al, 2012;Martina et al, 2008;Shimojima et al, 2014) and integrin ␣v␤3 (Bogachek et al, 2010;Fields et al, 2013;Perera-Lecoin et al, 2014;Smit et al, 2011;Zaitsev et al, 2014). Following attachment, the virus is then internalized into the cytoplasm via clathrin-mediated endocytosis (Brinton, 2014;Chu and Ng, 2004;Fields et al, 2013).…”