scholarly journals The Incorporation of Host Proteins into the External HIV-1 Envelope

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 85 ◽  
Author(s):  
Jonathan Burnie ◽  
Christina Guzzo
Keyword(s):  
Lipid Membrane ◽  
Hiv Treatment ◽  
Biologically Active ◽  
Host Protein ◽  
Host Proteins ◽  
Novel Treatments ◽  
Treatment And Prevention ◽  
Viral Egress ◽  
Protein Incorporation ◽  
Hiv 1

The incorporation of biologically active host proteins into HIV-1 is a well-established phenomenon, particularly due to the budding mechanism of viral egress in which viruses acquire their external lipid membrane directly from the host cell. While this mechanism might seemingly imply that host protein incorporation is a passive uptake of all cellular antigens associated with the plasma membrane at the site of budding, this is not the case. Herein, we review the evidence indicating that host protein incorporation can be a selective and conserved process. We discuss how HIV-1 virions displaying host proteins on their surface can exhibit a myriad of altered phenotypes, with notable impacts on infectivity, homing, neutralization, and pathogenesis. This review describes the canonical and emerging methods to detect host protein incorporation, highlights the well-established host proteins that have been identified on HIV-1 virions, and reflects on the role of these incorporated proteins in viral pathogenesis and therapeutic targeting. Despite many advances in HIV treatment and prevention, there remains a global effort to develop increasingly effective anti-HIV therapies. Given the broad range of biologically active host proteins acquired on the surface of HIV-1, additional studies on the mechanisms and impacts of these incorporated host proteins may inform the development of novel treatments and vaccine designs.

Host protein incorporation is conserved among diverse HIV-1 subtypes

AIDS ◽  
1999 ◽  
Vol 13 (3) ◽  
pp. 425 ◽  
Author(s):  
B.D. Roberts ◽  
S.T. Butera
Keyword(s):  
Host Protein ◽  
Protein Incorporation ◽  
Hiv 1

scholarly journals Cellular and Biochemical Mechanisms of the Retroviral Restriction Factor SAMHD1

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Li Wu
Keyword(s):  
Host Protein ◽  
Nucleic Acid Metabolism ◽  
Target Cells ◽  
Restriction Factors ◽  
Host Proteins ◽  
Retroviral Infection ◽  
Deoxynucleoside Triphosphate ◽  
Biochemical Mechanisms ◽  
Hiv 1

Replication of HIV-1 and other retroviruses is dependent on numerous host proteins in the cells. Some of the host proteins, however, function as restriction factors to block retroviral infection of target cells. The host protein SAMHD1 has been identified as the first mammalian deoxynucleoside triphosphate triphosphohydrolase (dNTPase), which blocks the infection of HIV-1 and other retroviruses in non-cycling immune cells. SAMHD1 protein is highly expressed in human myeloid-lineage cells and CD4+ T-lymphocytes, but its retroviral restriction function is only observed in noncycling cells. Recent studies have revealed biochemical mechanisms of SAMHD1-mediated retroviral restriction. In this review, the latest progress on SAMHD1 research is summarized and the mechanisms by which SAMHD1 mediates retroviral restriction are analyzed. Although the physiological function of SAMHD1 is largely unknown, this review provides perspectives about the role of endogenous SAMHD1 protein in maintaining normal cellular function, such as nucleic acid metabolism and the proliferation of cells.

scholarly journals Identification of host proteins differentially associated with HIV-1 RNA splice variants

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Rachel Knoener ◽  
Edward Evans ◽  
Jordan T Becker ◽  
Mark Scalf ◽  
Bayleigh Benner ◽  
...  
Keyword(s):  
Splice Variants ◽  
Rna Stability ◽  
Host Protein ◽  
Host Proteins ◽  
Single Population ◽  
Mass Spectrometric Identification ◽  
Sirna Knockdown ◽  
Variant Protein ◽  
Hiv 1

HIV-1 generates unspliced (US), partially spliced (PS), and completely spliced (CS) classes of RNAs, each playing distinct roles in viral replication. Elucidating their host protein ‘interactomes’ is crucial to understanding virus-host interplay. Here, we present HyPR-MSSV for isolation of US, PS, and CS transcripts from a single population of infected CD4+ T-cells and mass spectrometric identification of their in vivo protein interactomes. Analysis revealed 212 proteins differentially associated with the unique RNA classes, including preferential association of regulators of RNA stability with US and PS transcripts and, unexpectedly, mitochondria-linked proteins with US transcripts. Remarkably, >80 of these factors screened by siRNA knockdown impacted HIV-1 gene expression. Fluorescence microscopy confirmed several to co-localize with HIV-1 US RNA and exhibit changes in abundance and/or localization over the course of infection. This study validates HyPR-MSSV for discovery of viral splice variant protein interactomes and provides an unprecedented resource of factors and pathways likely important to HIV-1 replication.

scholarly journals The Promise of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are the Data?

2021 ◽  
Vol 20 ◽  
pp. 232595822110090
Author(s):  
Kimberly K. Scarsi ◽  
Susan Swindells
Keyword(s):  
Medication Adherence ◽  
Antiretroviral Therapy ◽  
Hiv Treatment ◽  
Virologic Suppression ◽  
Social Barriers ◽  
Treatment And Prevention ◽  
Undetectable Viremia ◽  
Long Acting ◽  
Available Information ◽  
Living With Hiv

As with other chronic conditions, adherence to daily medications remains a challenge for many individuals living with HIV due to structural, behavioral, and social barriers. Unfortunately, high levels of adherence to antiretroviral therapy are required to maintain virologic suppression. Alternative approaches are being explored to decrease the burden of daily pill administration, including long-acting injectable, oral, and implantable products. Phase 3 data support the efficacy of nanoformulated injectable cabotegravir and rilpivirine for HIV treatment in patients with undetectable viremia, but we have yet to learn how this strategy may benefit those with medication adherence challenges. Despite this, the affected community and HIV providers are very interested in exploring the role of long-acting therapies to address some types of barriers to medication adherence. This review summarizes available information about the potential for long-acting therapy to improve adherence for some patients and outlines associated opportunities and challenges with the implementation of long-acting therapy for the treatment and prevention of HIV.

scholarly journals Analysis of Low-Frequency Mutations Associated with Drug Resistance to Raltegravir before Antiretroviral Treatment

2010 ◽  
Vol 55 (3) ◽  
pp. 1114-1119 ◽  
Author(s):  
Jia Liu ◽  
Michael D. Miller ◽  
Robert M. Danovich ◽  
Nathan Vandergrift ◽  
Fangping Cai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Failure ◽  
Low Frequency ◽  
Hiv Treatment ◽  
Viral Population ◽  
Virologic Suppression ◽  
Resistance Mutations ◽  
The Difference ◽  
Allele Specific Sequencing ◽  
Hiv 1

ABSTRACTRaltegravir is highly efficacious in the treatment of HIV-1 infection. The prevalence and impact on virologic outcome of low-frequency resistant mutations among HIV-1-infected patients not previously treated with raltegravir have not been fully established. Samples from HIV treatment-experienced patients entering a clinical trial of raltegravir treatment were analyzed using a parallel allele-specific sequencing (PASS) assay that assessed six primary and six secondary integrase mutations. Patients who achieved and sustained virologic suppression (success patients,n= 36) and those who experienced virologic rebound (failure patients,n= 35) were compared. Patients who experienced treatment failure had twice as many raltegravir-associated resistance mutations prior to initiating treatment as those who achieved sustained virologic success, but the difference was not statistically significant. The frequency of nearly all detected resistance mutations was less than 1% of viral population, and the frequencies of mutations between the success and failure groups were similar. Expansion of pre-existing mutations (one primary and five secondary) was observed in 16 treatment failure patients in whom minority resistant mutations were detected at baseline, suggesting that they might play a role in the development of drug resistance. Two or more mutations were found in 13 patients (18.3%), but multiple mutations were not present in any single viral genome by linkage analysis. Our study demonstrates that low-frequency primary RAL-resistant mutations were uncommon, while minority secondary RAL-resistant mutations were more frequently detected in patients naïve to raltegravir. Additional studies in larger populations are warranted to fully understand the clinical implications of these mutations.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus Nonstructural Protein 2 Interacts with a Host Protein Complex Involved in Mitochondrial Biogenesis and Intracellular Signaling

2009 ◽  
Vol 83 (19) ◽  
pp. 10314-10318 ◽  
Author(s):  
Cromwell T. Cornillez-Ty ◽  
Lujian Liao ◽  
John R. Yates ◽  
Peter Kuhn ◽  
Michael J. Buchmeier
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Intracellular Signaling ◽  
Nonstructural Protein ◽  
Host Protein ◽  
Nonstructural Proteins ◽  
Host Proteins ◽  
Catalytic Activities ◽  
Nonstructural Protein 2 ◽  
Host Signaling ◽  
Prohibitin 1

ABSTRACT The severe acute respiratory syndrome coronavirus (SARS-CoV) generates 16 nonstructural proteins (nsp's) through proteolytic cleavage of a large precursor protein. Although several nsp's exhibit catalytic activities that are important for viral replication and transcription, other nsp's have less clearly defined roles during an infection. In order to gain a better understanding of their functions, we attempted to identify host proteins that interact with nsp's during SARS-CoV infections. For nsp2, we identified an interaction with two host proteins, prohibitin 1 (PHB1) and PHB2. Our results suggest that nsp2 may be involved in the disruption of intracellular host signaling during SARS-CoV infections.

scholarly journals SimpactCyan 1.0: An Open-source Simulator for Individual-Based Models in HIV Epidemiology with R and Python Interfaces

2018 ◽  
Author(s):  
Jori Liesenborgs ◽  
Diana M Hendrickx ◽  
Elise Kuylen ◽  
David Niyukuri ◽  
Niel Hens ◽  
...  
Keyword(s):  
Open Source ◽  
Hiv Infections ◽  
Hiv Treatment ◽  
Model Parameters ◽  
Eligibility Criteria ◽  
Hiv Epidemiology ◽  
Treatment And Prevention ◽  
Individual Based Models ◽  
Prevention Programmes ◽  
The Impact

ABSTRACTSimpactCyan is an open-source simulator for individual-based models in HIV epidemiology. Its core algorithm is written in C++ for computational efficiency, while the R and Python interfaces aim to make the tool accessible to the fast-growing community of R and Python users. Transmission, treatment and prevention of HIV infections in dynamic sexual networks are simulated by discrete events. A generic “intervention” event allows model parameters to be changed over time, and can be used to model medical and behavioural HIV prevention programmes. First, we describe a more efficient variant of the modified Next Reaction Method that drives our continuous-time simulator. Next, we outline key built-in features and assumptions of individual-based models formulated in SimpactCyan, and provide code snippets for how to formulate, execute and analyse models in SimpactCyan through its R and Python interfaces. Lastly, we give two examples of applications in HIV epidemiology: the first demonstrates how the software can be used to estimate the impact of progressive changes to the eligibility criteria for HIV treatment on HIV incidence. The second example illustrates the use of SimpactCyan as a data-generating tool for assessing the performance of a phylodynamic inference framework.

scholarly journals SWTICH DE ESQUEMAS ANTIRRETROVIRAIS DURANTE A PANDEMIA DE COVID-19 EM UM CENTRO DE REFERÊNCIA DA AMÉRICA LATINA

RAHIS ◽  
2021 ◽  
Vol 18 (4) ◽  
pp. 168-169
Author(s):  
Dirce Inês Silva ◽  
Isabela Estrela Santos ◽  
Jaqueline Xavier Oliveira
Keyword(s):  
Research Society ◽  
Hiv Treatment ◽  
Services Research ◽  
Prevention Services ◽  
Treatment And Prevention ◽  
The Social ◽  
America Latina ◽  
Terapia Antirretroviral ◽  
The Impact ◽  
Brazilian Journal

INTRODUÇÃO : O tratamento da infecção pelo vírus da imunodeficiência humana (HIV) é realizado por meio da terapia antirretroviral (TARV) e vem apresentando avanços importantes no decorrer dos anos. Ocorreu a introdução de novas drogas e classes que ampliaram de modo significativo as opções para o tratamento da infecção pelo HIV-1. Existem razões para a troca (Swtich) da TARV, são eles : manutenção da supressão viral, resistência, probabilidade de maior adesão ao tratamento, eventos adversos, interações medicamentosas (1). Durante a pandemia de Covid-19 que vivenciamos desde março de 2020 no Brasil muitas dificuldades ocorreram nos serviços de saúde, principalmente para as pessoas que vivem com HIV como : acesso aos serviços, diagnóstico, tratamento e acompanhamento (2.3). OBJETIVO: Avaliar a prevalência de trocas de esquemas em um centro de referência da América Latina no período de Janeiro de 2020 a 31 de Julho de 2021.METODOLOGIA : Realizamos um estudo transversal no período de 2020 a 2021 , utilizando o sistema de informação : Sistema de Controle Logístico de Medicamentos (SICLOM) do Ministério da Saúde . Os dados foram analisados no Statistical Package for the Social Science(SPSS® ) 22.RESULTADOS : No período do estudo foram detectadas 473 trocas. Em 2020 ocorreram 283 trocas, 83 em mulheres e 200 em homens. E 2021 até o dia 31/07/2021 foram detectadas 190 trocas, 76 ocorreram em mulheres e 114 em homens. As trocas ocorreram devido : resistência, reações adversas, gestação , tratamento concomitante da tuberculose e simplificação do tratamento ( Figura 1 e 2)).   Figura 1 – Ocorências de Swtich de esquemas antirretroviraisFigura 2- Razões de Trocas de Esquemas Antiretrovirais CONCLUSÃO : Swtich dos esquemas antirretrovirais em utilização pode ser uma estratégia de simplificação da TARV, melhoria da adesão, e em muitos casos a redução de eventos adversos. O arsenal terapêutico no contexto brasileiro é diversificado permitindo uma troca com segurança e sem risco de perda da eficácia virológica. Sendo uma estratégia para enfrentamento da infecção pelo HIV mesmo em tempos de pandemia do COVID19. REFERÊNCIAS:1-Brites, Carlos. Terapia antirretroviral atual: tendências e desafios. Estratégias de troca (switch) naterapia antirretroviral atual. Brazilian Journal of Infectious DiseaseVol 2 . Nº 1 . Fevereiro 20162- Moura, Maria Lucia Costa de. (2020). Coronavírus e COVID-19. Revista Saúde Coletiva, 53, 10.3- Parente, J. da S.; Azevedo, S. L. de .; Moreira, L. da F. A.; Abreu, L. M. .; Souza, L. V. de. The impact of social isolation on the COVID-19 pandemic on access to HIV treatment and prevention services. Research, Society and Development, [S. l.], v. 10, n. 1, p. e28110111692, 2021.  

scholarly journals More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Alison F Feder ◽  
Soo-Yon Rhee ◽  
Susan P Holmes ◽  
Robert W Shafer ◽  
Dmitri A Petrov ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Treatment ◽  
Adaptive Mutation ◽  
Selective Sweeps ◽  
Resistance Mutations ◽  
Consensus Sequences ◽  
Adaptive Mutations ◽  
Slow Evolution ◽  
Effective Drugs ◽  
Hiv 1

In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.

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