Cocaine and HIV Infection

Cardozo, Timothy; Shmelkov, Sergey V.; Rotrosen, John; Mateu‐Gelabert, Pedro; Friedman, Samuel R.

doi:10.1007/978-3-319-23150-1_6

Cited by 4 publications

(3 citation statements)

References 109 publications

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“…This finding provides a structural basis for hypothesizing that the epitope targeted by the MN-specific, RV144-vaccine-elicited, protection-associated Abs is conserved across circulating HIV strains. Indeed, independent evidence suggests that some protective Abs observed in the RV144 trial react with an Ab-targeted epitope that is conserved across multiple HIV subtypes[8, 29]. …”

Section: Discussionmentioning

confidence: 99%

“…The two others were secondary study variables: a gp120 peptide microarray and an ELISA using a non-biotinylated peptide equivalent to the V2 segment from positions 161 to 183 (numbering based on the Hxbc2 reference strain of HIV) of the MN strain of HIV (MN peptide) as the detection reagent [6]. Neither of these two latter probes were glycosylated entities, so they contained only natural amino acids, and they overlapped at the V2 peptide segment from positions 165 to 181[8, 9]. Two independent sieve analysis of RV144 data identified position 169 within this segment as correlating with vaccine efficacy, one of which identified a specific HLA allele/cytotoxic T-cell epitope (CTL) in the MN peptide [10, 11].…”

Section: Introductionmentioning

confidence: 99%

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Peptide Targeted by Human Antibodies Associated with HIV Vaccine-Associated Protection Assumes a Dynamic α-Helical Structure

et al. 2017

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The only evidence of vaccine-induced protection from HIV acquisition in humans was obtained in the RV144 HIV vaccine clinical trial. One immune correlate of risk in RV144 was observed to be higher titers of vaccine-induced antibodies (Abs) reacting with a 23-mer non-glycosylated peptide with the same amino acid sequence as a segment in the second variable (V2) loop of the MN strain of HIV. We used NMR to analyze the dynamic 3D structure of this peptide. Distance restraints between spatially proximate inter-residue protons were calculated from NOE cross peak intensities and used to constrain a thorough search of all possible conformations of the peptide. α–helical folding was strongly preferred by part of the peptide. A high-throughput structure prediction of this segment in all circulating HIV strains demonstrated that α–helical conformations are preferred by this segment almost universally across all subtypes. Notably, α–helical conformations of this segment of the V2 loop cluster cross-subtype-conserved amino acids on one face of the helix and the variable amino acid positions on the other in a semblance of an amphipathic α–helix. Accordingly, some Abs that protected against HIV in RV144 may have targeted a specific, conserved α–helical peptide epitope in the V2 loop of HIV’s surface envelope glycoprotein.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Peptide Targeted by Human Antibodies Associated with HIV Vaccine-Associated Protection Assumes a Dynamic α-Helical Structure

et al. 2017

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“…This suggests that the mechanism by which G614 viruses causes greater fatality is immunologic rather than virologic: namely, that the form that binds the receptor less well is also better shielded from host immune system attack and/or elicits harmful antiviral-spike antibodies or other harmful immune responses. Indeed, there are several precedents in other viral diseases: the viral spikes of both HIV and RSV exhibit unliganded states that do not elicit protective antibodies via vaccination, and indeed, may elicit antibodies that enhance disease 6,7 . Furthermore, diseaseenhancing, immunodominant, antibody-targeted epitopes in the SARS viral spike have been definitively identified 8 , and a recent report emphasized that key cryptic antibody-targeted neutralization epitopes in the SARS family of viral spikes are accessible only in the conformation in which the ACE-2 binding site is exposed 9 .…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate

Becerra-Flores

Cardozo²

Authorea

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Aim: The COVID pandemic is caused by infection with the SARS-CoV-2 virus. The major mutation detected to date in the SARS-CoV-2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation. Result: Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible. Conclusion: These results imply that G614 is a more pathogenic strain of SARS-CoV-2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID-19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection. What is known about this topic? Nothing is known about the health significance of the D614G SARS-CoV-2 variant. What does this article add? A molecular clue to viral molecular pathogenesis of COVID-19 disease.

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Illegale Drogen: Welche Arten gibt es und was sind ihre Eigenschaften?

Yesil¹

2021

Drogen Haben Kurze Beine

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Cocaine and HIV Infection

Cited by 4 publications

References 109 publications

Peptide Targeted by Human Antibodies Associated with HIV Vaccine-Associated Protection Assumes a Dynamic α-Helical Structure

Peptide Targeted by Human Antibodies Associated with HIV Vaccine-Associated Protection Assumes a Dynamic α-Helical Structure

SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate

Illegale Drogen: Welche Arten gibt es und was sind ihre Eigenschaften?

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