scholarly journals In Vitro Characterization of Adult Primary Human Immunodeficiency Virus Type 1: Demonstration of Distinctive Single‐Cell Killing Phenotypes in Spite of Similar Levels of Viral Replication

1997 ◽  
Vol 176 (4) ◽  
pp. 933-940 ◽  
Author(s):  
Achintya Pal ◽  
Thomas C. Greenough ◽  
John L. Sullivan ◽  
Mohan Somasundaran
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Single Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
In Vitro Characterization ◽  
Immunodeficiency Virus

Construction and in vitro characterization of a molecularly cloned human immunodeficiency virus type 1 library

Vaccine ◽  
2002 ◽  
Vol 20 (7-8) ◽  
pp. 1181-1185 ◽  
Author(s):  
Tetsu Mukai ◽  
Takeshi Kurosu ◽  
Masanobu Kinomoto ◽  
Satoshi Komoto ◽  
Miki Shiraga ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
In Vitro Characterization ◽  
Immunodeficiency Virus

scholarly journals Nef Binds p6* in GagPol during Replication of Human Immunodeficiency Virus Type 1

2004 ◽  
Vol 78 (10) ◽  
pp. 5311-5323 ◽  
Author(s):  
Luciana J. Costa ◽  
Yong-Hui Zheng ◽  
Jerica Sabotic ◽  
Johnson Mak ◽  
Oliver T. Fackler ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Virion Production ◽  
Immunodeficiency Virus ◽  
Intermediate Compartment ◽  
Hiv 1

ABSTRACT The atypical Nef protein (NefF12) from human immunodeficiency virus type 1 strain F12 (HIV-1F12) interferes with virion production and infectivity via a mysterious mechanism. The correlation of these effects with the unusual perinuclear subcellular localization of NefF12 suggested that the wild-type Nef protein could bind to assembly intermediates in late stages of viral replication. To test this hypothesis, Nef from HIV-1NL4-3 was fused to an endoplasmic reticulum (ER) retention signal (NefKKXX). This mutant NefKKXX protein recapitulated fully the effects of NefF12 on Gag processing and virion production, either alone or as a CD8 fusion protein. Importantly, the mutant NefKKXX protein also localized to the intermediate compartment, between the ER and the trans-Golgi network. Furthermore, Nef bound the GagPol polyprotein in vitro and in vivo. This binding mapped to the C-terminal flexible loop in Nef and the transframe p6* protein in GagPol. The significance of this interaction was demonstrated by a genetic assay in which the release of a mutant HIV-1 provirus lacking the PTAP motif in the late domain that no longer binds Tsg101 was rescued by a Nef.Tsg101 chimera. Importantly, this rescue as well as incorporation of Nef into HIV-1 virions correlated with the ability of Nef to interact with GagPol. Our data demonstrate that the retention of Nef in the intermediate compartment interferes with viral replication and suggest a new role for Nef in the production of HIV-1.

scholarly journals Modulation of Different Human Immunodeficiency Virus Type 1 Nef Functions during Progression to AIDS

2001 ◽  
Vol 75 (8) ◽  
pp. 3657-3665 ◽  
Author(s):  
Silke Carl ◽  
Thomas C. Greenough ◽  
Mandy Krumbiegel ◽  
Michael Greenberg ◽  
Jacek Skowronski ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Independent Functions ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) Nef protein has several independent functions that might contribute to efficient viral replication in vivo. Since HIV-1 adapts rapidly to its host environment, we investigated if different Nef properties are associated with disease progression. Functional analysis revealed thatnef alleles obtained during late stages of infection did not efficiently downmodulate class I major histocompatibility complex but were highly active in the stimulation of viral replication. In comparison, functional activity in downregulation of CD4 and enhancement of HIV-1 infectivity were maintained or enhanced after AIDS progression. Our results demonstrate that various Nef activities are modulated during the course of HIV-1 infection to maintain high viral loads at different stages of disease progression. These findings suggest that all in vitro Nef functions investigated contribute to AIDS pathogenesis and indicate that nef variants with increased pathogenicity emerge in a significant number of HIV-1-infected individuals.

scholarly journals Impact of Human Immunodeficiency Virus Type 1 Resistance to Protease Inhibitors on Evolution of Resistance to the Maturation Inhibitor Bevirimat (PA-457)

2009 ◽  
Vol 83 (10) ◽  
pp. 4884-4894 ◽  
Author(s):  
Catherine S. Adamson ◽  
Kayoko Waki ◽  
Sherimay D. Ablan ◽  
Karl Salzwedel ◽  
Eric O. Freed
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Single Amino Acid ◽  
Resistance Mutations ◽  
Immunodeficiency Virus ◽  
Maturation Inhibitor

ABSTRACT The maturation inhibitor bevirimat [3-O-(3′,3′dimethysuccinyl)betulinic acid; BVM; also known as PA-457 or DSB] potently inhibits human immunodeficiency virus type 1 (HIV-1) replication by blocking protease (PR)-mediated cleavage at the junction between capsid (CA) and spacer peptide 1 (SP1) in Gag. We previously isolated a panel of single-amino-acid substitutions that confer resistance to BVM in vitro (C. S. Adamson, S. D. Ablan, I. Boeras, R. Goila-Gaur, F. Soheilian, K. Nagashima, F. Li, K. Salzwedel, M. Sakalian, C. T. Wild, and E. O. Freed, J. Virol. 80:10957-10971, 2006). The BVM resistance mutations cluster at or near the CA-SP1 cleavage site. Because BVM likely will be used clinically in patients harboring viruses resistant to PR inhibitors (PIs), in this study we evaluated the interplay between a PI-resistant (PIR) PR and the BVM resistance mutations in Gag. As expected, the PIR mutations had no effect on inhibition by BVM; however, we observed general processing defects and a slight delay in viral replication in Jurkat T cells associated with the PIR mutations, even in the absence of compound. When combined, most BVM resistance and PIR mutations acted additively to impair viral replication, particularly in the presence of BVM. The BVM-resistant mutant SP1-A1V was an exception, as it supported robust replication in the context of either wild-type (WT) or PIR PR, even at high BVM concentrations. Significantly, the emergence of BVM resistance was delayed in the context of the PIR PR, and the SP1-A1V mutation was acquired most frequently with either WT or PIR PR. These results suggest that resistance to BVM is less likely to emerge in patients who have failed PIs than in patients who are PI naïve. We predict that the SP1-A1V substitution is the most likely to emerge in vivo, as this mutant replicates robustly independently of PR mutations or BVM. These findings offer insights into the effect of PIR mutations on the evolution of BVM resistance in PI-experienced patients.

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