Random Expression of Human Immunodeficiency Virus-1 (HIV-1) pl7 (Epitopes) on the Surface of the HIV-1-Infected Cell

Ota, Akemi; Liu, Xiaoliang; Fujio, Hajime; Sakato, Nobuo; Ueda, Shigeharu

doi:10.1089/hyb.1998.17.73

Cited by 13 publications

(10 citation statements)

References 6 publications

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“…Immunofluorescence staining of HIV-1-infected cell lines showed that different antigenic regions of p17 were found to be randomly expressed on the outer leaflet of live cell plasma membrane during HIV-1 replication4950. In particular, at least three regions of p17 (aa.12–29, 53–87, 87–115) were constantly detected on the cell surface by different anti-p17 mAbs, used as specific reagents, whereas other epitopes, even conformational, were occasionally expressed.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, at least three regions of p17 (aa.12–29, 53–87, 87–115) were constantly detected on the cell surface by different anti-p17 mAbs, used as specific reagents, whereas other epitopes, even conformational, were occasionally expressed. Based on the evidence that these mAbs lacked HIV-1 neutralizing activity, the authors concluded that the reactive epitopes of p17 were not the portions of viral protein in the virion itself, but more likely short polypeptide chains of p17 transported to the surface of HIV-1-infected cells50. More interestingly, p17 secretion has been hypothesized also in patients undergoing successful cART, since the viral protein was easily detected at nM concentration in the blood of cART-treated HIV-1-seropositive patients16.…”

Section: Discussionmentioning

confidence: 99%

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Cellular aspartyl proteases promote the unconventional secretion of biologically active HIV-1 matrix protein p17

Caccuri

Iaria

Campilongo

et al. 2016

Sci Rep

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The human immune deficiency virus type 1 (HIV-1) matrix protein p17 (p17), although devoid of a signal sequence, is released by infected cells and detected in blood and in different organs and tissues even in HIV-1-infected patients undergoing successful combined antiretroviral therapy (cART). Extracellularly, p17 deregulates the function of different cells involved in AIDS pathogenesis. The mechanism of p17 secretion, particularly during HIV-1 latency, still remains to be elucidated. A recent study showed that HIV-1-infected cells can produce Gag without spreading infection in a model of viral latency. Here we show that in Gag-expressing cells, secretion of biologically active p17 takes place at the plasma membrane and occurs following its interaction with phosphatidylinositol-(4,5)-bisphosphate and its subsequent cleavage from the precursor Gag (Pr55Gag) operated by cellular aspartyl proteases. These enzymes operate a more complex Gag polypeptide proteolysis than the HIV-1 protease, thus hypothetically generating slightly truncated or elongated p17s in their C-terminus. A 17 C-terminal residues excised p17 was found to be structurally and functionally identical to the full-length p17 demonstrating that the final C-terminal region of p17 is irrelevant for the protein’s biological activity. These findings offer new opportunities to identify treatment strategies for inhibiting p17 release in the extracellular microenvironment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cellular aspartyl proteases promote the unconventional secretion of biologically active HIV-1 matrix protein p17

Caccuri

Iaria

Campilongo

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Proteins were resolved by SDS–polyacrylamide gels (4–12%) and transferred to nitrocellulose membranes by using iBlot (Invitrogen). The membranes were treated with mouse anti-MA monoclonal antibody (29), mouse anti-CA monoclonal antibody (Advanced Biotechnologies Inc., Columbia, MD, USA), rabbit anti-NC polyclonal antibody, and rabbit anti-p6 polyclonal antibody (30). ECL Western blotting detection reagents (Nacalai Tesque, Kyoto, Japan) were used for signal detection with horseradish peroxidase conjugated anti-mouse and anti-rabbit IgG (Vector Laboratories, Burlingame, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

The relationship between HIV-1 genome RNA dimerization, virion maturation and infectivity

Ohishi

Nakano

Sakuragi

et al. 2010

Nucleic Acids Research

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The relationship between virion protein maturation and genomic RNA dimerization of human immunodeficiency virus type 1 (HIV-1) remains incompletely understood. We have constructed HIV-1 Gag cleavage site mutants to enable the steady state observation of virion maturation steps, and precisely study Gag processing, RNA dimerization, virion morphology and infectivity. Within the virion maturation process, the RNA dimer stabilization begins during the primary cleavage (p2-NC) of Pr55 Gag. However, the primary cleavage alone is not sufficient, and the ensuing cleavages are required for the completion of dimerization. From our observations, the increase of cleavage products may not put a threshold on the transition from fragile to stable dimeric RNA. Most of the RNA dimerization process did not require viral core formation, and particle morphology dynamics during viral maturation did not completely synchronize with the transition of dimeric RNA status. Although the endogenous virion RT activity was fully acquired at the initial step of maturation, the following process was necessary for viral DNA production in infected cell, suggesting the maturation of viral RNA/protein plays critical role for viral infectivity other than RT process.

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“…39,40 The viral protein sequence contains T cell epitopes, which are relatively conserved across different HIV-1 clades. 41 Further, the discovery of p17 epitopes on the surface of HIV-1 infected cells 42 suggests that p17 epitopes are potentially promising antigenic candidates for inclusion in a vaccine strategy. The objective of the present study was also to identify an efficient AT20-KLH plus p17 vaccination…”

Section: Discussionmentioning

confidence: 99%

Preclinical studies on immunogenicity of the HIV‐1 p17‐based synthetic peptide AT20‐KLH

et al. 2004

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Several studies have suggested that HIV-1 p17 matrix protein may play an important role in AIDS pathogenesis, since anti-p17 antibodies represent a serological marker of disease progression during HIV-1 infection both in adults and children. Moreover, it has been recently reported that the viral protein is capable of significantly increasing the proliferation of preactivated T lymphocytes and the release of proinflammatory cytokines. Recombinant HIV-1 p17 also has induced an increased rate of HIV-1 replication in vitro. All p17 biological activities are exerted after its binding to a specific cellular receptor expressed on activated T lymphocytes. The functional p17 epitope involved in receptor binding was found to be located at the NH(2)-terminal region of the viral protein. Immunization of C57BL/6 mice with a 20 amino acid synthetic peptide representative of the HIV-1 p17 functional region (AT20) coupled to the carrier protein keyhole limpet hemocyanin (KLH) and given in Freund's incomplete adjuvant, resulted in the development of p17-neutralizing antibodies capable of blocking p17/p17 receptor interaction, and consequently, all biological activities of the viral protein. Moreover, it was possible to skew the humoral response induced by priming mice with AT20-KLH toward cell-mediated immune responses, boosting animals with p17. Our findings may provide a new strategy to develop a synthetic AIDS vaccine based on a potentially effective and safe subunit vaccine against the HIV-1 cytokine-like matrix protein p17. Preclinical immunogenicity data for AT20-KLH provide the basis for evaluation of the peptide-based vaccine, alone and in combination with p17 or p17 DNA vaccines, in Phase I clinical trials.

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Random Expression of Human Immunodeficiency Virus-1 (HIV-1) pl7 (Epitopes) on the Surface of the HIV-1-Infected Cell

Cited by 13 publications

References 6 publications

Cellular aspartyl proteases promote the unconventional secretion of biologically active HIV-1 matrix protein p17

Cellular aspartyl proteases promote the unconventional secretion of biologically active HIV-1 matrix protein p17

The relationship between HIV-1 genome RNA dimerization, virion maturation and infectivity

Preclinical studies on immunogenicity of the HIV‐1 p17‐based synthetic peptide AT20‐KLH

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