scholarly journals Influence of Random Genetic Drift on Human Immunodeficiency Virus Type 1envEvolution During Chronic Infection

Genetics ◽  
2004 ◽  
Vol 166 (3) ◽  
pp. 1155-1164 ◽  
Author(s):  
Daniel Shriner ◽  
Raj Shankarappa ◽  
Mark A. Jensen ◽  
David C. Nickle ◽  
John E. Mittler ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Genetic Drift ◽  
Chronic Infection ◽  
Random Genetic Drift ◽  
Immunodeficiency Virus

scholarly journals Human Immunodeficiency Virus Type 1 V1-to-V5 Envelope Variants from the Chronic Phase of Infection Use CCR5 and Fuse More Efficiently than Those from Early after Infection

2009 ◽  
Vol 83 (19) ◽  
pp. 9694-9708 ◽  
Author(s):  
Behzad Etemad ◽  
Angela Fellows ◽  
Brenda Kwambana ◽  
Anupa Kamat ◽  
Yang Feng ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Chronic Infection ◽  
Early Infection ◽  
Replication Capacity ◽  
Ccr5 Receptor ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein modifications over the course of infection have been associated with coreceptor switching and antibody neutralization resistance, but the effect of the changes on replication and host cell receptor usage remains unclear. To examine this question, unique early- and chronic-stage infection envelope V1-toV5 (V1-V5) segments from eight HIV-1 subtype A-infected subjects were incorporated into an isogenic background to construct replication-competent recombinant viruses. In all subjects, viruses with chronic-infection V1-V5 segments showed greater replication capacity than those with early-infection V1-V5 domains in cell lines with high levels of both the CD4 and the CCR5 receptors. Viruses with chronic-infection V1-V5s demonstrated a significantly increased ability to replicate in cells with low CCR5 receptor levels and greater resistance to CCR5 receptor and fusion inhibitors compared to those with early-infection V1-V5 segments. These properties were associated with sequence changes in the envelope V1-V3 segments. Viruses with the envelope segments from the two infection time points showed no significant difference in their ability to infect cells with low CD4 receptor densities, in their sensitivity to soluble CD4, or in their replication capacity in monocyte-derived macrophages. Our results suggest that envelope changes, primarily in the V1-V3 domains, increase both the ability to use the CCR5 receptor and fusion kinetics. Thus, envelope modifications over time within a host potentially enhance replication capacity.

scholarly journals Parallel Human Immunodeficiency Virus Type 1-Specific CD8+ T-Lymphocyte Responses in Blood and Mucosa during Chronic Infection

2005 ◽  
Vol 79 (7) ◽  
pp. 4289-4297 ◽  
Author(s):  
F. Javier Ibarrondo ◽  
Peter A. Anton ◽  
Marie Fuerst ◽  
Hwee L. Ng ◽  
Johnson T. Wong ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
T Lymphocyte ◽  
Chronic Infection ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Ctl Responses

ABSTRACT Gut-associated lymphoid tissue is the major reservoir of lymphocytes and human immunodeficiency virus type 1 (HIV-1) replication in vivo, yet little is known about HIV-1-specific CD8+ T-lymphocyte (CTL) responses in this compartment. Here we assessed the breadth and magnitude of HIV-1-specific CTL in the peripheral blood and sigmoid colon mucosa of infected subjects not on antiretroviral therapy by enzyme-linked immunospot analysis with 53 peptide pools spanning all viral proteins. Comparisons of blood and mucosal CTL revealed that the magnitude of pool-specific responses is correlated within each individual (mean r 2 = 0.82 ± 0.04) and across all individuals (r 2 = 0.75; P < 0.001). Overall, 85.1% of screened peptide pools yielded concordant negative or positive results between compartments. CTL targeting was also closely related between blood and mucosa, with Nef being the most highly targeted (mean of 2.4 spot-forming cells [SFC[/106 CD8+ T lymphocytes/amino acid [SFC/CD8/aa]), followed by Gag (1.5 SFC/CD8/aa). Finally, comparisons of peptide pool responses seen in both blood and mucosa (concordant positives) versus those seen only in one but not the other (discordant positives) showed that most discordant results were likely an artifact of responses being near the limit of detection. Overall, these results indicate that HIV-1-specific CTL responses in the blood mirror those seen in the mucosal compartment in natural chronic infection. For protective or immunotherapeutic vaccination, it will be important to determine whether immunity is elicited in the mucosa, which is a key site of initial infection and subsequent HIV-1 replication in vivo.

scholarly journals Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1

Virology ◽  
2010 ◽  
Vol 396 (2) ◽  
pp. 339-348 ◽  
Author(s):  
Avishek Nandi ◽  
Christine L. Lavine ◽  
Pengcheng Wang ◽  
Inna Lipchina ◽  
Paul A. Goepfert ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Chronic Infection ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Immunodeficiency Virus

scholarly journals Independent Evolution of Human Immunodeficiency Virus Type 1 env V1/V2 and V4/V5 Hypervariable Regions during Chronic Infection

2007 ◽  
Vol 81 (10) ◽  
pp. 5413-5417 ◽  
Author(s):  
Patrick R. Harrington ◽  
Julie A. E. Nelson ◽  
Kathryn M. Kitrinos ◽  
Ronald Swanstrom
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Chronic Infection ◽  
Human Subjects ◽  
Hypervariable Regions ◽  
Single Genome ◽  
Immunodeficiency Virus ◽  
Multiple Blood

ABSTRACT Using DNA heteroduplex tracking assays, we characterized human immunodeficiency virus type 1 env V4/V5 genetic populations in multiple blood plasma samples collected over an average of 7 months from 24 chronically infected human subjects. We observed complex and dynamic V4/V5 genetic populations in most subjects. Comparisons of V4/V5 and V1/V2 population changes over the course of the study showed that major shifts in genetic populations frequently occurred in one region but not the other, and these observations were independently confirmed in one subject by single-genome sequencing. These results suggest that the V1/V2 and V4/V5 regions of env often evolve independently during chronic infection.

scholarly journals Primary Virus Envelope Cross-Reactivity of the Broadening Neutralizing Antibody Response during Early Chronic Human Immunodeficiency Virus Type 1 Infection

1999 ◽  
Vol 73 (6) ◽  
pp. 5225-5230 ◽  
Author(s):  
Peng Fei Zhang ◽  
Xi Chen ◽  
Da Wei Fu ◽  
Joseph B. Margolick ◽  
Gerald V. Quinnan
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Chronic Infection ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Time Points ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT To test the hypothesis that changing neutralizing antibody responses against human immunodeficiency virus type 1 (HIV-1) during chronic infection were a response to emergence of neutralization escape mutants, we cloned expressed and characterized envelope clones from patients in the Multicenter AIDS Cohort Study (MACS). Pseudotyped HIV-1 envelope clones obtained from differing time points were assessed for sensitivity to neutralization by using sera from different times from the same and different patients. Clones from early and late time points during chronic infection had similar neutralization sensitivity, and neutralizing antibody responses cross-reacted with early, late, and heterologous envelopes. The potential for broadly effective HIV-1 immunization is supported.

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