HIV-1 Vaccine Strategies Utilizing Viral Vectors Including Antigen- Displayed Inoviral Vectors

2014 ◽  
Vol 11 (8) ◽  
pp. 610-622 ◽  
Author(s):  
Kyriakos Hassapis ◽  
Leondios Kostrikis
Keyword(s):  
Viral Vectors ◽  
Hiv 1

scholarly journals A stronger transcription regulatory circuit of HIV-1C drives the rapid establishment of latency with implications for the direct involvement of Tat

2020 ◽  
Author(s):  
Sutanuka Chakraborty ◽  
Manisha Kabi ◽  
Udaykumar Ranga
Keyword(s):  
Transcription Factor ◽  
Viral Infection ◽  
Viral Vectors ◽  
Transcription Factor Binding ◽  
Jurkat Cells ◽  
Subtype C ◽  
Viral Promoter ◽  
Factor Binding ◽  
Transcriptional Silence ◽  
Hiv 1

AbstractThe magnitude of transcription factor binding site variation emerging in HIV-1C, especially the addition of NF-κB motifs by sequence duplication, makes the examination of transcriptional silence challenging. How can HIV-1 establish and maintain latency despite having a strong LTR? We constructed panels of sub-genomic reporter viral vectors with varying copy numbers of NF-κB motifs (0 to 4 copies) and examined the profile of latency establishment in Jurkat cells. We found surprisingly that the stronger the viral promoter, the faster the latency establishment. Importantly, at the time of commitment to latency and subsequent points, Tat levels in the cell were not limiting. Using highly sensitive strategies, we demonstrate the presence of Tat in the latent cell, recruited to the latent LTR. Our data allude, for the first time, to Tat establishing a negative feedback loop during the late phases of viral infection, leading to the rapid silencing of the viral promoter.ImportanceOver the past 10-15 years, HIV-1C has been evolving rapidly towards gaining stronger transcriptional activity by sequence duplication of major transcription factor binding sites. The duplication of NF-κB motifs is unique and exclusive for HIV-1C, a property not shared with any of the other eight HIV-1 genetic families. What mechanism(s) does HIV-1C employ to establish and maintain transcriptional silence despite the presence of a strong promoter and a concomitant strong, positive transcriptional feedback is the primary question we attempted to address in the present manuscript. The role Tat plays in latency reversal is well established. Our work with the most common HIV-1 subtype C (HIV-1C) offers crucial leads towards Tat possessing a dual-role in serving both as transcriptional activator and repressor at different phases of the viral infection of the cell. The leads we offer through the present work have significant implications for HIV-1 cure research.

scholarly journals Sequence Determinants in Gammaretroviral Env Cytoplasmic Tails Dictate Virus-Specific Pseudotyping Compatibility

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Yul Eum Song ◽  
Grace Y. Olinger ◽  
Sanath Kumar Janaka ◽  
Marc C. Johnson
Keyword(s):  
Viral Vectors ◽  
Leukemia Virus ◽  
Target Cells ◽  
Gag Protein ◽  
Factors Affecting ◽  
Gene Therapies ◽  
Viral Glycoproteins ◽  
Cytoplasmic Tails ◽  
Specific Manner ◽  
Hiv 1

ABSTRACTViruses can incorporate foreign glycoproteins to form infectious particles through a process known as pseudotyping. However, not all glycoproteins are compatible with all viruses. Despite the fact that viral pseudotyping is widely used, what makes a virus/glycoprotein pair compatible is poorly understood. To study this, we chose to analyze a gammaretroviral glycoprotein (Env) whose compatibility with different viruses could be modulated through small changes in its cytoplasmic tail (CT). One form of this glycoprotein is compatible with murine leukemia virus (MLV) particles but incompatible with human immunodeficiency virus type 1 (HIV-1) particles, while the second is compatible with HIV-1 particles but not with MLV particles. To decipher the factors affecting virus-specific Env incompatibility, we characterized Env incorporation, maturation, cell-to-cell fusogenicity, and virus-to-cell fusogenicity of each Env. The HIV-1 particle incompatibility correlated with less efficient cleavage of the R peptide by HIV-1 protease. However, the MLV particle incompatibility was more nuanced. MLV incompatibility appeared to be caused by lack of incorporation into particles, yet incorporation could be restored by further truncating the CT or by using a chimeric MLV Gag protein containing the HIV-1 MA without fully restoring infectivity. The MLV particle incompatibility appeared to be caused in part by fusogenic repression in MLV particles through an unknown mechanism. This study demonstrates that the Env CT can dictate functionality of Env within particles in a virus-specific manner.IMPORTANCEViruses utilize viral glycoproteins to efficiently enter target cells during infection. How viruses acquire viral glycoproteins has been studied to understand the pathogenesis of viruses and develop safer and more efficient viral vectors for gene therapies. The CTs of viral glycoproteins have been shown to regulate various stages of glycoprotein biogenesis, but a gap still remains in understanding the molecular mechanism of glycoprotein acquisition and functionality regarding the CT. Here, we studied the mechanism of how specific mutations in the CT of a gammaretroviral envelope glycoprotein distinctly affect infectivity of two different viruses. Different mutations caused failure of glycoproteins to function in a virus-specific manner due to distinct fusion defects, suggesting that there are virus-specific characteristics affecting glycoprotein functionality.

scholarly journals A Zigzag but Upward Way to Develop an HIV-1 Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 511
Author(s):  
Ziyu Wen ◽  
Caijun Sun
Keyword(s):  
Viral Vectors ◽  
Protective Efficacy ◽  
Effective Vaccine ◽  
Immunological Parameters ◽  
Recombinant Viruses ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Immunodeficiency Virus ◽  
Hiv 1

After decades of its epidemic, the human immunodeficiency virus type 1 (HIV-1) is still rampant worldwide. An effective vaccine is considered to be the ultimate strategy to control and prevent the spread of HIV-1. To date, hundreds of clinical trials for HIV-1 vaccines have been tested. However, there is no HIV-1 vaccine available yet, mostly because the immune correlates of protection against HIV-1 infection are not fully understood. Currently, a variety of recombinant viruses-vectored HIV-1 vaccine candidates are extensively studied as promising strategies to elicit the appropriate immune response to control HIV-1 infection. In this review, we summarize the current findings on the immunological parameters to predict the protective efficacy of HIV-1 vaccines, and highlight the latest advances on HIV-1 vaccines based on viral vectors.

Construction and characterisation of replicating foamy viral vectors expressing HIV-1 epitopes recognised by broadly neutralising antibodies

2013 ◽  
Vol 100 (2) ◽  
pp. 314-320 ◽  
Author(s):  
Michael Mühle ◽  
Kerstin Hoffmann ◽  
Martin Löchelt ◽  
Joachim Denner
Keyword(s):  
Viral Vectors ◽  
Neutralising Antibodies ◽  
Hiv 1

Therapeutic vaccination against HIV: current progress and future possibilities

2005 ◽  
Vol 110 (1) ◽  
pp. 59-71 ◽  
Author(s):  
Rebekah L. Puls ◽  
Sean Emery
Keyword(s):  
Antiretroviral Therapy ◽  
Viral Vectors ◽  
Therapeutic Vaccine ◽  
Viral Disease ◽  
Clear Understanding ◽  
Therapeutic Vaccination ◽  
Expensive Drug ◽  
Drug Regimens ◽  
Anti Hiv ◽  
Hiv 1

Although effective in reducing mortality, current antiretroviral therapy for HIV infection involves complex and expensive drug regimens that are toxic and difficult to take. Eradication of HIV reservoirs is not possible with existing therapies. The concept of therapeutic vaccination has been investigated to increase the potency and breadth of anti-HIV immune responses in order to delay or reduce antiretroviral therapy use. A variety of approaches targeted to both cell- and antibody-mediated immunity have been developed, including whole inactivated HIV-1, protein subunits and synthetic peptides, DNA vaccines and a number of viral vectors expressing HIV-1. These investigations have occurred in the absence of a clear understanding of disease pathogenesis or the correlates of protective immunity. At this time, there is no licensed therapeutic vaccine for any viral disease, including HIV; however, this review will consider recent progress in the field and summarize the challenges faced in the development of a therapeutic HIV vaccine.

scholarly journals Viral vectors as potential HIV-1 vaccines

2001 ◽  
Vol 200 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Matthias J Schnell
Keyword(s):  
Viral Vectors ◽  
Hiv 1

Optimizing HIV-1-specific CD8+ T-cell induction by recombinant BCG in prime-boost regimens with heterologous viral vectors

2011 ◽  
Vol 41 (12) ◽  
pp. 3542-3552 ◽  
Author(s):  
Richard Hopkins ◽  
Anne Bridgeman ◽  
Charles Bourne ◽  
Alice Mbewe-Mvula ◽  
Jerald C. Sadoff ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Vectors ◽  
Cd8 T Cell ◽  
Cell Induction ◽  
Hiv 1 ◽  
Recombinant Bcg

scholarly journals A Stronger Transcription Regulatory Circuit of HIV-1C Drives the Rapid Establishment of Latency with Implications for the Direct Involvement of Tat

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Sutanuka Chakraborty ◽  
Manisha Kabi ◽  
Udaykumar Ranga
Keyword(s):  
Transcription Factor ◽  
Viral Infection ◽  
Viral Vectors ◽  
Transcription Factor Binding ◽  
Jurkat Cells ◽  
Subtype C ◽  
Viral Promoter ◽  
Factor Binding ◽  
Transcriptional Silence ◽  
Hiv 1

ABSTRACT The magnitude of transcription factor binding site variation emerging in HIV-1 subtype C (HIV-1C), especially the addition of NF-κB motifs by sequence duplication, makes the examination of transcriptional silence challenging. How can HIV-1 establish and maintain latency despite having a strong long terminal repeat (LTR)? We constructed panels of subgenomic reporter viral vectors with varying copy numbers of NF-κB motifs (0 to 4 copies) and examined the profile of latency establishment in Jurkat cells. Surprisingly, we found that the stronger the viral promoter, the faster the latency establishment. Importantly, at the time of commitment to latency and subsequent points, Tat levels in the cell were not limiting. Using highly sensitive strategies, we demonstrate the presence of Tat in the latent cell, recruited to the latent LTR. Our data allude, for the first time, to Tat establishing a negative feedback loop during the late phases of viral infection, leading to the rapid silencing of the viral promoter. IMPORTANCE Over the past 10 to 15 years, HIV-1 subtype C (HIV-1C) has been evolving rapidly toward gaining stronger transcriptional activity by sequence duplication of major transcription factor binding sites. The duplication of NF-κB motifs is unique and exclusive to HIV-1C, a property not shared with any of the other eight HIV-1 genetic families. What mechanism(s) does HIV-1C employ to establish and maintain transcriptional silence despite the presence of a strong promoter and concomitant strong, positive transcriptional feedback is the primary question that we attempted to address in the present manuscript. The role that Tat plays in latency reversal is well established. Our work with the most common HIV-1 subtype, HIV-1C, offers crucial leads toward Tat possessing a dual role in serving as both a transcriptional activator and repressor at different phases of viral infection of the cell. The leads that we offer through the present work have significant implications for HIV-1 cure research.

scholarly journals Inhibition of Human Immunodeficiency Virus Type 1 Replication in Primary Macrophages by Using Tat- or CCR5-Specific Small Interfering RNAs Expressed from a Lentivirus Vector

2003 ◽  
Vol 77 (22) ◽  
pp. 11964-11972 ◽  
Author(s):  
Ming-Ta M. Lee ◽  
Glen A. Coburn ◽  
Myra O. McClure ◽  
Bryan R. Cullen
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Vectors ◽  
Expression Vectors ◽  
Small Interfering Rnas ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Although several groups have demonstrated that RNA interference, induced by transfection of small interfering RNA (siRNA) duplexes, can protect cells against a viral challenge in culture, this protection is transient. Here, we describe lentivirus expression vectors that can stably express siRNAs at levels sufficient to block virus replication. We have used these vectors to stably express siRNAs specific for the essential human immunodeficiency virus type 1 (HIV-1) Tat transcription factor or specific for a cellular coreceptor, CCR5, that is required for infection by the majority of primary HIV-1 isolates. These lentivirus vectors are shown to protect cells, including primary macrophages, against HIV-1 infection in culture by inducing selective degradation of their target mRNA species. These data suggest that it should be possible to block the expression of specific viral or cellular genes in vivo by using viral vectors to stably express the appropriate siRNAs.

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