Immunising with the transmembrane envelope proteins of different retroviruses including HIV-1

Denner, Joachim

doi:10.4161/hv.23221

Cited by 22 publications

(23 citation statements)

References 73 publications

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“…For porcine endogenous retrovirus (PERV) and feline leukemia virus (FeLV), the transmembrane (TM) protein p15E and the surface (SU) protein gp70, which are parts of the viral envelope, have been tested for their potential for immunizing the host species (Denner et al, 2012; Kaulitz et al, 2011; Langhammer et al, 2011; Waechter et al, 2013). Gammaretrovirus envelope proteins are less variable than those of HIV-1 (Denner, 2013; Mansky and Temin, 1995). Immunization studies with the envelope proteins of gammaretroviruses PERV, FELV and KoRV across mammalian species have consistently obtained neutralizing antibodies.…”

Section: Introductionmentioning

confidence: 99%

Sequence variation of koala retrovirus transmembrane protein p15E among koalas from different geographic regions

et al. 2015

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The koala retrovirus (KoRV), which is transitioning from an exogenous to an endogenous form, has been associated with high mortality in koalas. For other retroviruses, the envelope protein p15E has been considered a candidate for vaccine development. We therefore examined proviral sequence variation of KoRV p15E in a captive Queensland and three wild southern Australian koalas. We generated 163 sequences with intact open reading frames, which grouped into 39 distinct haplotypes. Sixteen distinct haplotypes comprising 139 of the sequences (85%) coded for the same polypeptide. Among the remaining 23 haplotypes, 22 were detected only once among the sequences, and each had 1 or 2 non-synonymous differences from the majority sequence. Several analyses suggested that p15E was under purifying selection. Important epitopes and domains were highly conserved across the p15E sequences and in previously reported exogenous KoRVs. Overall, these results support the potential use of p15E for KoRV vaccine development.

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Section: Introductionmentioning

confidence: 99%

Sequence variation of koala retrovirus transmembrane protein p15E among koalas from different geographic regions

et al. 2015

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“…when immunising with the same batches of PERV rp15E (Keller et al, 2014) and gp70/rp52 (unpublished data). Although binding and neutralising antibodies against KoRV-A rp15E and gp70/rp52 was readily induced by immunising goats, mice and rats (Fiebig et al, 2006;Denner, 2012Denner, , 2014, it is presently unknown whether immunisation of koalas with recombinant KoRV proteins will result in the production of antibodies neutralising KoRV-A and KoRV-B. It is also unclear whether koalas that are tolerant to KoRV-A are able to produce antibodies to KoRV-B, based on the differences in the receptor-binding site in gp70.…”

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confidence: 99%

Lack of antiviral antibody response in koalas infected with koala retroviruses (KoRV)

et al. 2015

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“…In HIV-1, this 22 amino acid peptide is involved in the incorporation of Env proteins into the membrane, allows membrane fusion, promotes viral infectivity and finally the MPER region is also an immunogenic peptide [67,68,69,70]. The N659D substitution could potentially have an impact on the HIV-2 predicted MPER functions.…”

Section: Discussionmentioning

confidence: 99%

Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism

Dufrasne

Lombard

Goubau

et al. 2016

Viruses

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BST-2 or tetherin is a host cell restriction factor that prevents the budding of enveloped viruses at the cell surface, thus impairing the viral spread. Several countermeasures to evade this antiviral factor have been positively selected in retroviruses: the human immunodeficiency virus type 2 (HIV-2) relies on the envelope glycoprotein (Env) to overcome BST-2 restriction. The Env gp36 ectodomain seems involved in this anti-tetherin activity, however residues and regions interacting with BST-2 are not clearly defined. Among 32 HIV-2 ROD Env mutants tested, we demonstrated that the asparagine residue at position 659 located in the gp36 ectodomain is mandatory to exert the anti-tetherin function. Viral release assays in cell lines expressing BST-2 showed a loss of viral release ability for the HIV-2 N659D mutant virus compared to the HIV-2 wild type virus. In bst-2 inactivated H9 cells, those differences were lost. Subtilisin treatment of infected cells demonstrated that the N659D mutant was more tethered at the cell surface. Förster resonance energy transfer (FRET) experiments confirmed a direct molecular link between Env and BST-2 and highlighted an inability of the mutant to bind BST-2. We also tested a virus presenting a truncation of 109 amino acids at the C-terminal part of Env, a cytoplasmic tail partial deletion that is spontaneously selected in vitro. Interestingly, viral release assays and FRET experiments indicated that a full Env cytoplasmic tail was essential in BST-2 antagonism. In HIV-2 infected cells, an efficient Env-mediated antagonism of BST-2 is operated through an intermolecular link involving the asparagine 659 residue as well as the C-terminal part of the cytoplasmic tail.

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Immunising with the transmembrane envelope proteins of different retroviruses including HIV-1

Cited by 22 publications

References 73 publications

Sequence variation of koala retrovirus transmembrane protein p15E among koalas from different geographic regions

Sequence variation of koala retrovirus transmembrane protein p15E among koalas from different geographic regions

Lack of antiviral antibody response in koalas infected with koala retroviruses (KoRV)

Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism

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