scholarly journals Exploring the potential of group II introns to inactivate human immunodeficiency virus type 1

2008 ◽  
Vol 89 (10) ◽  
pp. 2605-2610 ◽  
Author(s):  
Reza Nazari ◽  
Sadhna Joshi
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Group Ii Intron ◽  
Progeny Virus ◽  
Immunodeficiency Virus ◽  
Group Ii ◽  
Hiv 1

This study examined whether insertion of a mobile group II intron into infectious human immunodeficiency virus type 1 (HIV-1) provirus DNA could inhibit virus replication. Introns targeted against two sites within the integrase-coding region were used. The intron-inserted HIV-1 provirus DNA clones were isolated and tested for virus replication. Similar amounts of HIV-1 RNA, Gag protein and progeny virus were produced from HIV-1 provirus DNA and intron-inserted HIV-1 provirus DNA. However, when the progeny virus was tested for its infectivity, although the group II intron-inserted HIV-1 RNA was packaged and reverse-transcribed, the dsDNA failed to integrate, as expected in the absence of a functional integrase, and virus replication was aborted. These results demonstrate that group II introns can confer ‘complete’ inhibition of HIV-1 replication at the intended step and should be further exploited for HIV-1 gene therapy and other targeted genetic repairs.

scholarly journals Structure–functional analysis of human immunodeficiency virus type 1 (HIV-1) Vpr: role of leucine residues on Vpr-mediated transactivation and virus replication

Virology ◽  
2004 ◽  
Vol 328 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Dineshkumar Thotala ◽  
Elizabeth A. Schafer ◽  
Biswanath Majumder ◽  
Michelle L. Janket ◽  
Marc Wagner ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals Incorporation of HLA-DR into the Envelope of Human Immunodeficiency Virus Type 1 In Vivo: Correlation with Stage of Disease and Presence of Opportunistic Infection

2000 ◽  
Vol 74 (21) ◽  
pp. 10256-10259 ◽  
Author(s):  
Stephen D. Lawn ◽  
Salvatore T. Butera
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Active Tuberculosis ◽  
Hla Dr ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) bearing HLA-DR in its envelope was detected in plasma from all patients with chronic HIV-1 infection (n = 16) and was present at higher levels in patients with active tuberculosis coinfection (n = 6). Intriguingly, however, HLA-DR was not detectable in HIV-1 from patients during primary viremia (n = 6), suggesting the possibility of virus replication in less-activated cells.

scholarly journals DNA Vaccines against Human Immunodeficiency Virus Type 1 in the Past Decade

2004 ◽  
Vol 17 (2) ◽  
pp. 370-389 ◽  
Author(s):  
Malavika Giri ◽  
Kenneth E. Ugen ◽  
David B. Weiner
Keyword(s):  
Human Immunodeficiency Virus ◽  
Animal Models ◽  
Disease Progression ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Control Virus ◽  
Hiv 1

SUMMARY This article reviews advances in the field of human immunodeficiency virus type 1 (HIV-1) and AIDS vaccine development over the last decade, with an emphasis on the DNA vaccination approach. Despite the discovery of HIV-1 and AIDS in humans nearly 20 years ago, there is no vaccine yet that can prevent HIV-1 infection. The focus has shifted toward developing vaccines that can control virus replication and disease progression by eliciting broadly cross-reactive T-cell responses. Among several approaches evaluated, the DNA-based modality has shown considerable promise in terms of its ability to elicit cellular immune responses in primate studies. Of great importance are efforts aimed at improvement of the potency of this modality in the clinic. The review discusses principles of DNA vaccine design and the various mechanisms of plasmid-encoded antigen presentation. The review also outlines current DNA-based vaccine strategies and vectors that have successfully been shown to control virus replication and slow disease progression in animal models. Finally, it lists recent strategies that have been developed as well as novel approaches under consideration to enhance the immunogenicity of plasmid-encoded HIV-1 antigen in various animal models.

scholarly journals G-Protein Signaling Triggered by R5 Human Immunodeficiency Virus Type 1 Increases Virus Replication Efficiency in Primary T Lymphocytes

2005 ◽  
Vol 79 (12) ◽  
pp. 7938-7941 ◽  
Author(s):  
Yea-Lih Lin ◽  
Clément Mettling ◽  
Pierre Portalès ◽  
Brigitte Réant ◽  
Jacques Clot ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocytes ◽  
G Protein ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cell Activation ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The binding of R5 envelope to CCR5 during human immunodeficiency virus type 1 (HIV-1) entry provokes cell activation, which has so far been considered to have no effect on virus replication, since signaling-defective CCR5 molecules have been shown to function normally as HIV-1 coreceptors on transformed cells or mitogen-stimulated T lymphocytes. As the background state of activation of these cells might have biased the results, we performed experiments using the same approach but with nonactivated primary T lymphocytes. We now report that the single R126N mutation in the DRY motif, involved in G-protein coupling, results in a signaling-defective CCR5 coreceptor with a drastically impaired capacity to support HIV-1 infection.

scholarly journals Genetic Instability of Live, Attenuated Human Immunodeficiency Virus Type 1 Vaccine Strains

1999 ◽  
Vol 73 (2) ◽  
pp. 1138-1145 ◽  
Author(s):  
Ben Berkhout ◽  
Koen Verhoef ◽  
Jeroen L. B. van Wamel ◽  
Nicole K. T. Back
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Vaccine Strain ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Ltr Promoter ◽  
Hiv 1

ABSTRACT Live, attenuated viruses have been the most successful vaccines in monkey models of human immunodeficiency virus type 1 (HIV-1) infection. However, there are several safety concerns about using such an anti-HIV vaccine in humans, including reversion of the vaccine strain to virulence and recombination with endogenous retroviral sequences to produce new infectious and potentially pathogenic viruses. Because testing in humans would inevitably carry a substantial risk, we set out to test the genetic stability of multiply deleted HIV constructs in perpetuated tissue culture infections. The Δ3 candidate vaccine strain of HIV-1 contains deletions in the viral long terminal repeat (LTR) promoter and the vpr and nef genes. This virus replicates with delayed kinetics, but a profound enhancement of virus replication was observed after approximately 2 months of culturing. Analysis of the revertant viral genome indicated that the three introduced deletions were maintained but a 39-nucleotide sequence was inserted in the LTR promoter region. This insert was formed by duplication of the region encoding three binding sites for the Sp1 transcription factor. The duplicated Sp1 region was demonstrated to increase the LTR promoter activity, and a concomitant increase in the virus replication rate was measured. In fact, duplication of the Sp1 sites increased the fitness of the Δ3 virus (Vpr/Nef/U3) to levels higher than that of the singly deleted ΔVpr virus. These results indicate that deleted HIV-1 vaccine strains can evolve into fast-replicating variants by multiplication of remaining sequence motifs, and their safety is therefore not guaranteed. This insight may guide future efforts to develop more stable anti-HIV vaccines.

scholarly journals The effect of cyclosporine A on infection of susceptible cells by human immunodeficiency virus type 1

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 1904-1910 ◽  
Author(s):  
MA Wainberg ◽  
A Dascal ◽  
N Blain ◽  
L Fitz-Gibbon ◽  
F Boulerice ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cyclosporine A ◽  
Peripheral Blood ◽  
Inhibitory Effect ◽  
Progeny Virus ◽  
Immunodeficiency Virus ◽  
Hiv 1

Abstract The effect of cyclosporine A (CyA) on the ability of the human immunodeficiency virus type 1 (HIV-1) to infect the H-9 T-cell leukemic line, as well as interleukin-2 (IL-2)-grown human peripheral blood- derived lymphocytes, has been studied. Pretreatment of H-9 cells and human lymphocytes with CyA over 24 hours completely prevented viral infection over a 21-day period, whereas the addition of drug at two hours postinfection with HIV-1 had a significant inhibitory effect on viral replication and expression of the virus-specific antigens p17 and p24. However, if CyA was added at later times to these lymphocytic cells, this inhibitory effect was lost. Indeed, the removal of CyA from cultures that had been treated from two hours after infection led to the rapid production of progeny virus. HIV-1 was able to infect peripheral blood lymphocytes obtained from each of four kidney allograft recipients on long-term CyA antirejection therapy, as long as drug was not included in the culture medium. In addition, we asked what effect pretreatment with CyA of cells of the U-937 monocytic line and primary cultures of human monocytes/macrophages might have on infection by HIV-1. CyA had no demonstrable effect on the ability of HIV-1 to infect cells of either type.

scholarly journals The effect of cyclosporine A on infection of susceptible cells by human immunodeficiency virus type 1

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 1904-1910
Author(s):  
MA Wainberg ◽  
A Dascal ◽  
N Blain ◽  
L Fitz-Gibbon ◽  
F Boulerice ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cyclosporine A ◽  
Peripheral Blood ◽  
Inhibitory Effect ◽  
Progeny Virus ◽  
Immunodeficiency Virus ◽  
Hiv 1

The effect of cyclosporine A (CyA) on the ability of the human immunodeficiency virus type 1 (HIV-1) to infect the H-9 T-cell leukemic line, as well as interleukin-2 (IL-2)-grown human peripheral blood- derived lymphocytes, has been studied. Pretreatment of H-9 cells and human lymphocytes with CyA over 24 hours completely prevented viral infection over a 21-day period, whereas the addition of drug at two hours postinfection with HIV-1 had a significant inhibitory effect on viral replication and expression of the virus-specific antigens p17 and p24. However, if CyA was added at later times to these lymphocytic cells, this inhibitory effect was lost. Indeed, the removal of CyA from cultures that had been treated from two hours after infection led to the rapid production of progeny virus. HIV-1 was able to infect peripheral blood lymphocytes obtained from each of four kidney allograft recipients on long-term CyA antirejection therapy, as long as drug was not included in the culture medium. In addition, we asked what effect pretreatment with CyA of cells of the U-937 monocytic line and primary cultures of human monocytes/macrophages might have on infection by HIV-1. CyA had no demonstrable effect on the ability of HIV-1 to infect cells of either type.

scholarly journals CD40-Mediated Induction of CD4 and CXCR4 on B Lymphocytes Correlates with Restricted Susceptibility to Human Immunodeficiency Virus Type 1 Infection: Potential Role of B Lymphocytes as a Viral Reservoir

1999 ◽  
Vol 73 (10) ◽  
pp. 7972-7980 ◽  
Author(s):  
Susan Moir ◽  
Réjean Lapointe ◽  
Angela Malaspina ◽  
Mario Ostrowski ◽  
Charsey E. Cole ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
B Lymphocytes ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Reservoir ◽  
Cxcr4 Usage ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) replicates primarily in lymphoid tissues where it has ready access to activated immune competent cells. We used one of the major pathways of immune activation, namely, CD40-CD40L interactions, to study the infectability of B lymphocytes isolated from peripheral blood mononuclear cells. Highly enriched populations of B lymphocytes generated in the presence of interleukin-4 and oligomeric soluble CD40L upregulated costimulatory and activation markers, as well as HIV-1 receptors CD4 and CXCR4, but not CCR5. By using single-round competent luciferase viruses complemented with either amphotropic or HIV-derived envelopes, we found a direct correlation between upregulation of HIV-1 receptors and the susceptibility of the B lymphocytes to infection with dual-tropic and T-tropic strains of HIV-1; in contrast, cells were resistant to M-tropic strains of HIV-1. HIV-1 envelope-mediated infection was completely abolished with either an anti-CD4 monoclonal antibody or a peptide known to directly block CXCR4 usage and partially blocked with stromal cell-derived factor 1, all of which had no effect on the entry of virus pseudotyped with amphotropic envelope. Full virus replication kinetics confirmed that infection depends on CXCR4 usage. Furthermore, productive cycles of virus replication occurred rapidly yet under most conditions, without the appearance of syncytia. Thus, an activated immunological environment may induce the expression of HIV-1 receptors on B lymphocytes, priming them for infection with selective strains of HIV-1 and allowing them to serve as a potential viral reservoir.

scholarly journals Second-Site Reversion of a Human Immunodeficiency Virus Type 1 Reverse Transcriptase Mutant That Restores Enzyme Function and Replication Capacity

1999 ◽  
Vol 73 (8) ◽  
pp. 6293-6298 ◽  
Author(s):  
Isabel Olivares ◽  
Víctor Sánchez-Merino ◽  
Miguel A. Martínez ◽  
Esteban Domingo ◽  
Cecilio López-Galíndez ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Progeny Virus ◽  
Replication Capacity ◽  
Nucleotide Sequence Analysis ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Nonconservative substitutions for Tyr-115 in the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) lead to enzymes displaying lower affinity for deoxynucleoside triphosphates (dNTPs) (A. M. Martı́n-Hernández, E. Domingo, and L. Menéndez-Arias, EMBO J. 15:4434–4442, 1996). Several mutations at this position (Y115W, Y115L, Y115A, and Y115D) were introduced in an infectious HIV-1 clone, and the replicative capacity of the mutant viruses was monitored. Y115W was the only mutant able to replicate in MT-4 cells, albeit very poorly. Nucleotide sequence analysis of the progeny virus recovered from supernatants of four independent transfection experiments showed that the Y115W mutation was maintained. However, in all cases an additional substitution in the primer grip of the RT (M230I) emerged when the virus increased its replication capacity. Using recombinant HIV-1 RT, we demonstrate that M230I mitigates the polymerase activity defect of the Y115W mutant, by increasing the dNTP binding affinity of the enzyme. The second-site suppressor effects observed were mediated by mutations in the 66-kDa subunit of the RT, as demonstrated with chimeric heterodimers. Examination of available crystal structures of HIV-1 RT suggests a possible mechanism for restoration of enzyme activity by the second-site revertant.

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