Inhibition of infectious human immunodeficiency virus type 1 particle formation by Gag protein-derived peptides

Niedrig, Matthias; Gelderblom, Hans R.; Pauli, Georg; März, Josefine; Bickhard, Heike; Wolf, Hans; Modrow, Susanne

doi:10.1099/0022-1317-75-6-1469

Cited by 47 publications

(38 citation statements)

References 24 publications

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“…However, the location o f the D203 deletion is adjacent to a conserved sequence identified by Poblotzki et al (1993) as essential for particle production. Peptides derived from this area o f G a g have been also reported to have antiviral activity when added to HIV-1 infected cultures (Niedrig et al, 1994). Our results suggest that the effect of such a peptide m a y be direct competition for a protein-protein contact site as has been shown for peptides from the p17 domain that exhibit similar properties (Morikawa et al, 1995).…”

Section: Discussionsupporting

confidence: 62%

Gag-Gag interactions in the C-terminal domain of human immunodeficiency virus type 1 p24 capsid antigen are essential for Gag particle assembly

Zhang¹,

Hockley

Nermut

et al. 1996

Journal of General Virology

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Seven internal deletions within the p24 domain of the human immunodeficiency virus type 1 Gag precursor have been assessed for their effect on Gag particle formation following their expression using recombinant baculoviruses. In addition, each deleted molecule was assessed for its ability to bind soluble p24 antigen in vitro. The mutants fell into three different phenotypic groups: (i) three mutants that had no effect on either p24 binding or Gag particle assembly, (ii) three mutants that abolished both features and (iii) one mutant that bound p24 in vitro but failed to assemble particles. Mutations that abolished both in vitro p24 binding and particle assembly mapped to the C terminus of p24 confirming this region as critical for virion assembly. We suggest the division of virion assembly into at least two distinct phases and suggest a model in which the critical sequences mapped to date are combined with available structural information.

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Section: Discussionsupporting

confidence: 62%

Gag-Gag interactions in the C-terminal domain of human immunodeficiency virus type 1 p24 capsid antigen are essential for Gag particle assembly

Zhang¹,

Hockley

Nermut

et al. 1996

Journal of General Virology

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“…These include the use of sense RNA (47,48), benzamides (49), peptides (50), antibodies (51) and dominant negative proteins (52). The RNAs described here may provide an alternative strategy for directly inhibiting gag protein function.…”

Section: Discussionmentioning

confidence: 99%

In vitro selection of RNAs that bind to the human immunodeficiency virus type-1 gag polyprotein

Lochrie

Waugh²,

Pratt³

et al. 1997

Nucleic Acids Research

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“…C6͞36 cells were infected with BTV (moi ϭ 5) and peptides added to the growth medium, as previously described (27). Supernatants were harvested 7 days postinfection and plaque assays performed by using BSR cells as described previously (28).…”

Section: Methodsmentioning

confidence: 99%

The membrane trafficking protein calpactin forms a complex with bluetongue virus protein NS3 and mediates virus release

Beaton

Rodrı́guez

Reddy

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

111

120

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Bluetongue virus, an arbovirus of the Orbivirus genus, infects and replicates in both insect and mammalian cells. However, the cytopathic effect (cpe) on each host is very different. Mammalian cells show substantial cpe, most likely a result of the mechanism of virus release, whereas insect cells show little cpe and appear to release virus without cell lysis. Expression analysis of each infected cell type shows one protein, the nonstructural (NS) protein NS3, to be differentially expressed in the different cell types, suggesting it may act in the virus egress pathway. The molecular basis of such an interaction, however, has never been clear. Here, by using yeast two-hybrid analysis, we show that NS3 interacts with a cellular protein p11 (calpactin light chain), part of the annexin II complex that is involved in exocytosis. We map the NS3 region of interaction with p11 to a 13-residue peptide found at the N terminus of the protein and show it effectively competes with p36 (annexin II heavy chain) for p11 ligand binding. Further, we show that the C-terminal domain of NS3 interacts with VP2, the outermost protein of the fully assembled virus particle, suggesting that NS3 forms a bridging molecule that draws assembled virus into contact with the cellular export machinery. Our data describe the first host protein involvement in orbivirus egress and provide new insights into understanding arbovirus interactions with their hosts.I nsect-borne arboviruses (arthropod-borne viruses), such as members of genus Orbivirus, are vectored to vertebrate species by arthropod species (e.g., gnats, mosquitoes, and ticks) and replicate in both hosts. However, whereas in vertebrate host cells these viruses cause severe cell damage, infections of insect cells are often inapparent. Bluetongue virus (BTV), the prototype virus of the genus Orbivirus, is transmitted by Culicoides spp., causing a disease of economical importance in the vertebrate hosts (ruminants) in many parts of the world. Other orbiviruses (14 serogroups within the genus, including African horse sickness virus and Epizootic hemorrhagic disease virus of deer) infect a variety of vertebrates, including humans, often causing severe diseases (1).Unlike the other arboviruses, BTV and other orbiviruses are nonenveloped and lack the glycosylated proteins known to facilitate both virus entry and exit processes. Consequently, orbiviruses are released from the infected cells predominantly by cell lysis (2, 3). However, BTV causes less severe cytopathic effects in insect vector cells despite highly efficient virus replication (4). BTV release from vector cells is nonlytic, and the virus particles leave the infected cell by passage, either individually or in groups, through a locally disrupted plasma membrane (5). However, the exact mechanism of cell-to-cell spread by the virus is not clear, and how the virus controls differential egress in insect and mammalian cells is one of the most intriguing aspects of BTV biology.BTV virions are architecturally complex icosahedral structures c...

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Inhibition of infectious human immunodeficiency virus type 1 particle formation by Gag protein-derived peptides

Cited by 47 publications

References 24 publications

Gag-Gag interactions in the C-terminal domain of human immunodeficiency virus type 1 p24 capsid antigen are essential for Gag particle assembly

Gag-Gag interactions in the C-terminal domain of human immunodeficiency virus type 1 p24 capsid antigen are essential for Gag particle assembly

In vitro selection of RNAs that bind to the human immunodeficiency virus type-1 gag polyprotein

The membrane trafficking protein calpactin forms a complex with bluetongue virus protein NS3 and mediates virus release

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