scholarly journals Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian–human immunodeficiency virus viraemia with protein/DNA combination

2008 ◽  
Vol 89 (2) ◽  
pp. 540-5533 ◽  
Author(s):  
Gerrit Koopman ◽  
Daniella Mortier ◽  
Sam Hofman ◽  
Nathalie Mathy ◽  
Marguerite Koutsoukos ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Current Data ◽  
Dna Immunization ◽  
Immunodeficiency Virus ◽  
Vaccine Antigens ◽  
Mixed Modality

Current data suggest that prophylactic human immunodeficiency virus type 1 (HIV) vaccines will be most efficacious if they elicit a combination of adaptive humoral and T-cell responses. Here, we explored the use of different vaccine strategies in heterologous prime–boost regimes and evaluated the breadth and nature of immune responses in rhesus monkeys induced by epidermally delivered plasmid DNA or recombinant HIV proteins formulated in the AS02A adjuvant system. These immunogens were administered alone or as either prime or boost in mixed-modality regimes. DNA immunization alone induced cell-mediated immune (CMI) responses, with a strong bias towards Th1-type cytokines, and no detectable antibodies to the vaccine antigens. Whenever adjuvanted protein was used as a vaccine, either alone or in a regime combined with DNA, high-titre antibody responses to all vaccine antigens were detected in addition to strong Th1- and Th2-type CMI responses. As the vaccine antigens included HIV-1 Env, Nef and Tat, as well as simian immunodeficiency virus (SIV)mac239 Nef, the animals were subsequently exposed to a heterologous, pathogenic simian–human immunodeficiency virus (SHIV)89.6p challenge. Protection against sustained high virus load was observed to some degree in all vaccinated groups. Suppression of virus replication to levels below detection was observed most frequently in the group immunized with protein followed by DNA immunization, and similarly in the group immunized with DNA alone. Interestingly, control of virus replication was associated with increased SIV Nef- and Gag-specific gamma interferon responses observed immediately following challenge.

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 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.

Synthetic CD4 exocyclics inhibit binding of human immunodeficiency virus type 1 envelope to CD4 and virus replication in T lymphocytes

1997 ◽  
Vol 15 (2) ◽  
pp. 150-154 ◽  
Author(s):  
Xin Zhang ◽  
Muriel Gaubin ◽  
Laurence Briant ◽  
Vasantha Srikantan ◽  
Ramachandran Murali ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocytes ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus

scholarly journals Human Immunodeficiency Virus Type 1 Integrase Protein Promotes Reverse Transcription through Specific Interactions with the Nucleoprotein Reverse Transcription Complex

1999 ◽  
Vol 73 (3) ◽  
pp. 2126-2135 ◽  
Author(s):  
Xiaoyun Wu ◽  
Hongmei Liu ◽  
Hongling Xiao ◽  
Joan A. Conway ◽  
Eric Hehl ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Reverse Transcription ◽  
Specific Interactions ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Integrase Protein

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) integrase protein (IN) is essential for integration of the viral DNA into host cell chromosomes. Since IN is expressed and assembled into virions as part of the 160-kDa Gag-Pol precursor polyprotein and catalyzes integration of the provirus in infected cells as a mature 32-kDa protein, mutations in IN are pleiotropic and may affect virus replication at different stages of the virus life cycle in addition to integration. Several different phenotypes have been observed for IN mutant viruses, including defects in virion morphology, protein composition, reverse transcription, nuclear import, and integration. Because the effects of mutations in the IN domain of Gag-Pol can not always be distinguished from those of mutations in the mature IN protein, there remains a significant gap in our understanding of IN function in vivo. To directly analyze the function of the mature IN protein itself, in the context of a replicating virus but independently from that of Gag-Pol, we used an approach developed in our laboratory for incorporating proteins into HIV virions by their expression in trans as fusion partners of either Vpr or Vpx. By providing IN intrans as a Vpr-IN fusion protein, our analysis revealed, for the first time, that the mature IN protein is essential for the efficient initiation of reverse transcription in infected cells and that this function does not require the IN protein to be enzymatically (integration) active. Our findings of a direct physical interaction between IN and reverse transcriptase and the failure of heterologous HIV-2 IN protein to efficiently support reverse transcription indicate that this novel function occurs through specific interactions with other viral components of the reverse transcription initiation complex. Studies involving complementation between integration- and DNA synthesis-defective IN mutants further support this conclusion and reveal that the highly conserved HHCC motif of IN is important for both activities. These findings provide important new insights into IN function and reverse transcription in the context of the nucleoprotein reverse transcription complex within the infected cell. Moreover, they validate a novel approach that obviates the need to mutate Gag-Pol in order to study the role of its individual mature components at the virus replication level.

scholarly journals Vif and the p55Gag Polyprotein of Human Immunodeficiency Virus Type 1 Are Present in Colocalizing Membrane-Free Cytoplasmic Complexes

1999 ◽  
Vol 73 (4) ◽  
pp. 2667-2674 ◽  
Author(s):  
James H. M. Simon ◽  
Elise A. Carpenter ◽  
Ron A. M. Fouchier ◽  
Michael H. Malim
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Protein Interactions ◽  
Subcellular Fractionation ◽  
Current Data ◽  
Protein Protein Interactions ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The Vif protein of human immunodeficiency virus type 1 (HIV-1) is a potent regulator of viral infectivity. Current data posit that Vif functions late in replication to modulate assembly, budding, and/or maturation. Consistent with this model, earlier indirect immunofluorescence analyses of HIV-1-infected cells demonstrated that Vif and Gag colocalize to a substantial degree (J. H. M. Simon, R. A. M. Fouchier, T. E. Southerling, C. B. Guerra, C. K. Grant, and M. H. Malim, J. Virol. 71:5259–5267, 1997). Here, we describe a series of subcellular fractionation studies which indicate that Vif and the p55Gag polyprotein are present in membrane-free cytoplasmic complexes that copurify in sucrose density gradients and are stable in nonionic detergents. Both Vif and Gag are targeted to these complexes independent of each other, and their association with them appears to be mediated by protein-protein interactions. We propose that these complexes may represent viral assembly intermediates and that Vif is appropriately localized to influence the final stages of the viral life cycle and, therefore, the infectivity of progeny virions.

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