Chaperones Involved in Hepatitis B Virus Morphogenesis

Abstract

Little is known about host cell factors necessary for hepatitis B virus (HBV) assembly which involves envelopment of cytosolic nucleocapsids by the S, M and L transmembrane viral envelope proteins and subsequent budding into intraluminal cisternae. Central to virogenesis is the L protein that mediates hepatocyte receptor binding and envelopment of capsids. To serve these topologically conflicting roles, L protein exhibits an unusual dual membrane topology, disposing its N-terminal preS domain inside and outside of the virion lipid envelope. The mixed topology is achieved by posttranslational preS translocation of about half of the L protein molecules across a post-endoplasmic reticulum membrane. Here we identify and characterize a preS-specific sequence that confers the suppression of cotranslational translocation even of a model reporter. This cytosolic anchorage sequence specifically binds the cognate heat shock protein Hsc70, thus indicating chaperone participitation in HBV morphogenesis. Conversely, the M envelope protein needs the assistance of the chaperone calnexin for proper folding and trafficking. Calnexin selectively binds to the N-glycan, specific for M, rather than to the N-glycan, common to all three envelope proteins. As inhibition of the calnexin-M interaction blocks the secretion of viral envelopes, we propose an essential role for calnexin, as well as for Hsc70, in chaperoning HBV assembly.

Assembly and budding of a hepatitis B virus is mediated by a novel type of intracellular vesicles

“…42 Thus, PDI in fractions 16 and 17 corresponds to the Golgi-associated protein. Immunoblotting of the subcellular fractions for the early endosomal marker protein Rab5B showed that endosomes were mainly present in the lighter fractions of the gradient (fractions [14][15][16][17] (Fig. 6).…”

“…Recently, some chaperones and ␥2-adaptin were identified as host factors participating in HBV progeny formation. [16][17][18] Viruses exploit a broad arsenal of strategies to assemble and bud within cells. For example, Pox-like, Irido-like, and Asfar-like viruses induce the formation of "aggresomes," which serve as scaffolds to concentrate structural components.…”

Differential Level of Host Gene Expression Associated with Nucleopolyhedrovirus Infection in Silkworm Races of Bombyx mori

“…Following SV40 or adenovirus type 5 infections, Hsc 70 was found to be the main virus-induced member of the Hsp70 family (Sainis et al, 1994). Hsc70 was found to interact with the L protein of hepatitis B virus, playing a crucial role in virus morphogenesis by regulating L protein translocation (Prange et al, 1999). Among heat shock proteins genes, in Hsp 20.4 transcript level was equal at 6 hpi in resistant and susceptible race and further constitutively expressed at low level in the resistant silkworm races up to 60 hpi.…”

The ER Glycoprotein Quality Control System

“…Combined factorsV and VIII deficiency (Nichols et al, 1998) Ergic-53 -Spondyloepiphyseal dysplasia tarda (Gedeon et al, 1999) SEDL (sedlin) -Viral Infections: Selected examples that are known to be associated with CNX/CRT quality control AIDS (Land and Braakman, 2001) 160/120 + CNX/CRT Herpes simplex-1 (Yamashita et al, 1996b) B, C and D + CNX/CRT Cytomegalovirus diseases (Yamashita et al, 1996a) B + CNX Influenza Haemagglutinin + CNX/CRT Hepatitis B (Prange et al, 1999) M + CNX Hepatitis C (Choukhi et al, 1998) E1 and E2 + CNX/CRT Rubella (Nakhasi et al, 2001) E1 and E2 + CNX/CRT Measles (Bolt, 2001) Haemagglutinin/Fusion + CNX/CRT Newcastle disease (McGinnes and Morrison, 1998) Haemagglutinin-neuraminidase + CNX Dengue hemorrhagic fever (Wu et al, 2002) M, E and NS1 + CNX Japanese encephalitis (Wu et al, 2002) M, E and NSI + CNX Uukiniemi virus infenction (Veijola and Pettersson, 1999) G1 and G2 + CNX/CRT Vesicular somatitis (Cannon et al, 1996) G + CNX/CRT δ where the defects are in the trimming and modification of the core oligosaccharide which had already been transferred to the target proteins.…”