Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Gag protein segment of human immunodeficiency virus 1 (HIV-1) has been fused to a C terminally truncated core antigen of hepatitis B virus (HBcAg) using an E. coli expression system. Fusion of 90 amino acids of HIV-1 Gag protein to HBcAg still allowed the formation of capsids presenting on their surface epitopes of HIV-1 core protein, whereas fusion of 317, 189, or 100 amino acids of Gag prevented self-assembly of chimeric particles. Mice immunized with recombinant particles emulsified with Freund's complete adjuvant (CFA) or aluminium hydroxide developed high anti-HBcAg titers. However, anti-HIVp24 antibodies were detected only in mice inoculated with immunogen emulsified with CFA.
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PMID:Immunogenicity of recombinant core particles of hepatitis B virus containing epitopes of human immunodeficiency virus 1 core antigen. 138 12

The Gag protein of human foamy virus (HFV) lacks Cys-His boxes present in the nucleocapsid (NC) domains of other retroviruses; instead it contains three glycine-arginine-rich motifs (GR boxes). We have expressed the carboxyl end of HFV Gag containing the GR boxes (the NC domain equivalent) and analyzed its nucleic acid binding properties. Our results show that the NC domain of HFV Gag binds with high affinity to both RNA and DNA, in a sequence-independent manner, as determined by filter binding assays. Analysis of a mutant containing a heterologous sequence in place of GR box I indicates that this motif is required for nucleic acid binding and for viral replication. A mutant in GR box II still binds to RNA and DNA in vitro, but virus containing this mutation does not replicate and no nuclear staining of the Gag protein is found in transfected cells. Surprisingly, a revertant from this mutant that completely lacks GR box II and exhibits very little nuclear transport of Gag can readily replicate in tissue culture. This finding thus provides a direct evidence that although the sequences in GR box II can serve as a nuclear transport signal, they are not required for HFV replication and it is unlikely that nuclear localization of Gag protein plays any critical role during viral infection. Taken together, our results suggest that the Gag protein of HFV may be more analogous to the core protein of the hepatitis B virus family than to conventional retroviral Gag protein.
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PMID:The carboxyl terminus of the human foamy virus Gag protein contains separable nucleic acid binding and nuclear transport domains. 897 Sep 44

Foamy virus (FV) replication is distinct from that of all other retroviruses in many respects, including viral assembly. In fact, the viral assembly pathway is rather similar to that of hepadnaviruses such as hepatitis B virus. Foamy virus Gag does not contain landmark retroviral assembly domains such as the major homology region, Cys-His boxes, or a defined M domain. Like hepadnaviruses, the FV Gag protein is not cleaved and contains arginine-rich regions at the carboxyl terminus. In addition, egress of FV particles requires presence of the envelope glycoproteins. Finally, the cis-acting sequences in the FV genome required for genome incorporation, although poorly defined, differ in location from other retroviruses.
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PMID:Particle assembly and genome packaging. 1290 69

Hepatitis B virus (HBV) is an enveloped DNA virus that presumably buds at intracellular membranes of infected cells. HBV budding involves two endocytic host proteins, the ubiquitin-interacting adaptor gamma 2-adaptin and the Nedd4 ubiquitin ligase. Here, we demonstrate that HBV release also requires the cellular machinery that generates internal vesicles of multivesicular bodies (MVBs). In order to perturb the MVB machinery in HBV-replicating liver cells, we used ectopic expression of dominant-negative mutants of different MVB components, like the ESCRT-III complex-forming CHMP proteins and the Vps4 ATPases. Upon coexpression of mutated CHMP3, CHMP4B, or CHMP4C forms, as well as of ATPase-defective Vps4A or Vps4B mutants, HBV assembly and egress were potently blocked. Each of the MVB inhibitors arrested virus particle maturation by entrapping the viral core and large and small envelope proteins in detergent-insoluble membrane structures that closely resembled aberrant endosomal class E compartments. In contrast, HBV subvirus particle release was not affected by MVB inhibitors, hinting at different export routes used by viral and subviral particles. To further define the role gamma 2-adaptin plays in HBV formation, we examined the effects of its overexpression in virus-replicating cells. Intriguingly, excess gamma 2-adaptin blocked HBV production in a manner similar to the actions of CHMP and Vps4 mutants. Moreover, overexpressed gamma 2-adaptin perturbed the endosomal morphology and diminished the budding of a retroviral Gag protein, implying that it may act as a principal inhibitor of the MVB sorting pathway. Together, these results demonstrate that HBV exploits the MVB machinery with the aid of gamma 2-adaptin.
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PMID:Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III, Vps4, and gamma 2-adaptin. 1755 70

Viral structural proteins are emerging as effective targets for new antivirals. In a viral lifecycle, the capsid must assemble, disassemble, and respond to host proteins, all at the right time and place. These reactions work within a narrow range of conditions, making them susceptible to small molecule interference. In at least three specific viruses, this approach has had met with preliminary success. In rhinovirus and poliovirus, compounds like pleconaril bind capsid and block RNA release. Bevirimat binds to Gag protein in HIV, inhibiting maturation. In Hepatitis B virus, core protein allosteric modulators (CpAMs) promote spontaneous assembly of capsid protein leading to empty and aberrant particles. Despite the biological diversity between viruses and the chemical diversity between antiviral molecules, we observe common features in these antivirals' mechanisms of action. These approaches work by stabilizing protein-protein interactions.
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PMID:Viral structural proteins as targets for antivirals. 3277 53