scholarly journals Balance between transmitted HLA preadapted and nonassociated polymorphisms is a major determinant of HIV-1 disease progression

2016 ◽  
Vol 213 (10) ◽  
pp. 2049-2063 ◽  
Author(s):  
Daniela C. Mónaco ◽  
Dario A. Dilernia ◽  
Andrew Fiore-Gartland ◽  
Tianwei Yu ◽  
Jessica L. Prince ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disease Progression ◽  
Major Determinant ◽  
Immune Recognition ◽  
Multivariable Model ◽  
Viral Control ◽  
New Host ◽  
Set Point ◽  
The Impact ◽  
Hiv 1

HIV-1 adapts to a new host through mutations that facilitate immune escape. Here, we evaluate the impact on viral control and disease progression of transmitted polymorphisms that were either preadapted to or nonassociated with the new host’s HLA. In a cohort of 169 Zambian heterosexual transmission pairs, we found that almost one-third of possible HLA-linked target sites in the transmitted virus Gag protein are already adapted, and that this transmitted preadaptation significantly reduced early immune recognition of epitopes. Transmitted preadapted and nonassociated polymorphisms showed opposing effects on set-point VL and the balance between the two was significantly associated with higher set-point VLs in a multivariable model including other risk factors. Transmitted preadaptation was also significantly associated with faster CD4 decline (<350 cells/µl) and this association was stronger after accounting for nonassociated polymorphisms, which were linked with slower CD4 decline. Overall, the relative ratio of the two classes of polymorphisms was found to be the major determinant of CD4 decline in a multivariable model including other risk factors. This study reveals that, even before an immune response is mounted in the new host, the balance of these opposing factors can significantly influence the outcome of HIV-1 infection.

scholarly journals How stress mediators can cumulatively contribute to Alzheimer’s disease An allostatic load approach

2019 ◽  
Vol 13 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Tatiane Martins Matos ◽  
Juliana Nery De Souza-Talarico
Keyword(s):  
Risk Factors ◽  
Cognitive Decline ◽  
Disease Progression ◽  
Chronic Stress ◽  
Allostatic Load ◽  
Stress Hormones ◽  
Modifiable Risk Factors ◽  
Cognitive Changes ◽  
Stress Mediators ◽  
The Impact

ABSTRACT. Allostatic load is defined as the frequent activation of the neuroendocrine, immunological, metabolic and cardiovascular systems, which makes individuals more susceptible to stress-related health problems. According to this model, physiological dysregulations start to emerge decades before diseases manifest. Consequently, stress research has shifted its attention to anticipating the degree of this dysregulation to better understand the impact of stress hormones and other biomarkers on disease progression. In view of the growing number of studies that demonstrate the influence of modifiable risk factors on cognitive decline, in addition to the effects of chronic stress mediators, the objective of the present review was to present an overview of the development of cognitive changes based on studies on stress and its mediators.

scholarly journals Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection

2012 ◽  
Vol 8 (3) ◽  
pp. e1002529 ◽  
Author(s):  
Matthew R. Henn ◽  
Christian L. Boutwell ◽  
Patrick Charlebois ◽  
Niall J. Lennon ◽  
Karen A. Power ◽  
...  
Keyword(s):  
Deep Sequencing ◽  
Acute Infection ◽  
Immune Recognition ◽  
Whole Genome ◽  
The Impact ◽  
Hiv 1

scholarly journals A Dual Infection/Competition Assay Shows a Correlation between Ex Vivo Human Immunodeficiency Virus Type 1 Fitness and Disease Progression

2000 ◽  
Vol 74 (19) ◽  
pp. 9222-9233 ◽  
Author(s):  
Miguel E. Quiñones-Mateu ◽  
Sarah C. Ball ◽  
Andre J. Marozsan ◽  
Vincent S. Torre ◽  
Jamie L. Albright ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Ex Vivo ◽  
Relative Fitness ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

ABSTRACT This study was designed to examine the impact of human immunodeficiency virus type 1 (HIV-1) fitness on disease progression through the use of a dual competition/heteroduplex tracking assay (HTA). Despite numerous studies on the impact of HIV-1 diversity and HIV-specific immune response on disease progression, we still do not have a firm understanding of the long-term pathogenesis of this virus. Strong and early CD8-positive cytotoxic T-cell and CD4-positive T-helper cell responses directed toward HIV-infected cells appear to curb HIV pathogenesis. However, the rate at which the virus infects the CD4+ T-cell population and possibly destroys the HIV-specific immune response may also alter the rate of disease progression. For HIV-1 fitness studies, we established conditions for dual HIV-1 infections of peripheral blood mononuclear cells (PBMC) and a sensitive HTA to measure relative virus production. A pairwise comparison was then performed to estimate the relative fitness of various non-syncytium-inducing/CCR5-tropic (NSI/R5) and syncytium-inducing/CXCR4-tropic (SI/X4) HIV-1 isolates. Four HIV-1 strains (two NSI/R5 and two SI/X4) with moderate ex vivo fitness were then selected as controls and competed against primary HIV-1 isolates from an HIV-infected Belgian cohort. HIV-1 isolates from long-term survivors (LTS) were outcompeted by control strains and were significantly less fit than HIV-1 isolates from patients with accelerated progression to AIDS (PRO). In addition, NSI/R5 HIV-1 isolates from PRO overgrew control SI/X4 strains, suggesting that not all SI/X4 HIV-1 isolates replicate more efficiently than all NSI/R5 isolates. Finally, there were strong, independent correlations between viral load and the total relative fitness values of HIV-1 isolates from PRO (r = 0.84, P = 0.033) and LTS (r = 0.86, P = 0.028). Separation of the PRO and LTS plots suggest that HIV-1 fitness together with viral load may be a strong predictor for the rate of disease progression.

scholarly journals Acute Plasma Biomarkers of T Cell Activation Set-Point Levels and of Disease Progression in HIV-1 Infection

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46143 ◽  
Author(s):  
Anne-Sophie Liovat ◽  
Marie-Anne Rey-Cuillé ◽  
Camille Lécuroux ◽  
Béatrice Jacquelin ◽  
Isabelle Girault ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Progression ◽  
T Cell Activation ◽  
Cell Activation ◽  
Set Point ◽  
Plasma Biomarkers ◽  
Hiv 1

scholarly journals Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring

2018 ◽  
Vol 69 (3) ◽  
pp. 523-529 ◽  
Author(s):  
Sharon A Riddler ◽  
Jennifer E Balkus ◽  
Urvi M Parikh ◽  
John W Mellors ◽  
Carolyne Akello ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Disease Progression ◽  
Virologic Failure ◽  
Vaginal Ring ◽  
Phase Iii ◽  
Virologic Suppression ◽  
Cell Counts ◽  
The Impact ◽  
Hiv 1

Abstract Background A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). Methods HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network–020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. Results Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42). Conclusions The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. Clinical Trials Registration NCT016170096 and NCT00514098.

scholarly journals The intra-host evolutionary and population dynamics of human immunodeficiency virus type 1: a phylogenetic perspective

2013 ◽  
Vol 5 (1S) ◽  
pp. 3 ◽  
Author(s):  
Marco Salemi
Keyword(s):  
Human Immunodeficiency Virus ◽  
Population Dynamics ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1 ◽  
Over Time

The intra-host evolutionary and population dynamics of the human immunodeficiency virus type 1 (HIV-1), the cause of the acquired immunodeficiency syndrome, have been the focus of one of the most extensive study efforts in the field of molecular evolution over the past three decades. As HIV-1 is among the fastest mutating organisms known, viral sequence data sampled over time from infected patients can provide, through phylogenetic analysis, significant insights about the tempo and mode of evolutionary processes shaped by complex interaction with the host milieu. Five main aspects are discussed: the patterns of HIV-1 intra-host diversity and divergence over time in relation to different phases of disease progression; the impact of selection on the temporal structure of HIV-1 intra-host genealogies inferred from longitudinally sampled viral sequences; HIV-1 intra-host sub-population structure; the potential relationship between viral evolutionary rate and disease progression and the central evolutionary role played by recombination occurring in super-infected cells.

scholarly journals The impact of HIV-1 within-host evolution on transmission dynamics

2017 ◽  
Author(s):  
Kristof Theys ◽  
Pieter Libin ◽  
Andrea-Clemencia Pineda-Pena ◽  
Ann Nowe ◽  
Anne-Mieke Vandamme ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Epidemiological Studies ◽  
Transmission Efficiency ◽  
Evolutionary Rates ◽  
New Host ◽  
Trade Off ◽  
Host Immune Responses ◽  
Host Evolution ◽  
The Impact ◽  
Hiv 1

AbstractThe adaptive potential of HIV-1 is a vital mechanism to evade host immune responses and antiviral treatment. However, high evolutionary rates during persistent infection can impair transmission efficiency and alter disease progression in the new host, resulting in a delicate trade-off between within-host virulence and between-host infectiousness. This trade-off is visible in the disparity in evolutionary rates at within-host and between-host levels, and preferential transmission of ancestral donor viruses. Understanding the impact of within-host evolution for epidemiological studies is essential for the design of preventive and therapeutic measures. Herein, we review recent theoretical and experimental work that generated new insights into the complex link between within-host evolution and between-host fitness, revealing temporal and selective processes underlying the structure and dynamics of HIV-1 transmission.

The role of viral coreceptors and enhanced macrophage tropism in human immunodeficiency virus type 1 disease progression

Sexual Health ◽  
2004 ◽  
Vol 1 (1) ◽  
pp. 23 ◽  
Author(s):  
Paul R. Gorry ◽  
Jasminka Sterjovski ◽  
Melissa Churchill ◽  
Kristie Witlox ◽  
Lachlan Gray ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Molecular Mechanisms ◽  
Coreceptor Usage ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

Despite numerous studies on the impact of viral diversity, human immunodeficiency virus type 1 (HIV-1)-specific immune responses and host factors on disease progression, we still do not have a firm understanding of the long-term pathogenesis of HIV-1 infection. Rapid depletion of CD4+ T-lymphocytes has been associated with a switch in viral coreceptor usage from CCR5 to CXCR4 in ~40 to 50% of infected individuals. However, the majority of infected individuals who progress to AIDS harbour only CCR5-dependent (R5) viral strains. The progression HIV-1 disease is associated with an enhanced tropism of R5 viral strains for monocyte/macrophage lineage cells (enhanced M-tropism). However, the underlying molecular mechanisms contributing to enhanced M-tropism by R5 HIV-1 strains, and how HIV-1 variants with enhanced M-tropism cause CD4+ T-cell depletion in vivo are unknown. This review examines the relationship between viral coreceptor usage, M-tropism, and pathogenicity of HIV-1. We highlight evidence supporting the hypothesis that enhanced M-tropism of R5 HIV-1 results from adaptive viral evolution, resulting in HIV-1 variants that have increased ability to utilise relatively low levels of CCR5 expressed on macrophages, by way of increased CCR5 affinity. The evidence also suggests that these late-emerging, R5 viral strains have reduced sensitivity to entry inhibitors, and increased ability to cause CD4+ T-lymphocyte loss. These variants are likely to impact HIV-1 disease progression, especially in patients who persistently harbour only R5 viral strains.

scholarly journals Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 423
Author(s):  
Zita Kruize ◽  
Ad C. van Nuenen ◽  
Stan W. van Wijk ◽  
Arginell F. Girigorie ◽  
Karel A. van Dort ◽  
...  
Keyword(s):  
Disease Progression ◽  
Class I Mhc ◽  
Mhc I ◽  
Surface Molecules ◽  
Histocompatibility Complex ◽  
Naturally Occurring ◽  
Multiple Amino Acid ◽  
The Impact ◽  
Increased Activity ◽  
Hiv 1

Nef is a multifunctional viral protein that has the ability to downregulate cell surface molecules, including CD4 and major histocompatibility complex class I (MHC-I) and, as recently shown, also members of the serine incorporator family (SERINC). Here, we analyzed the impact of naturally occurring mutations in HIV-1 Nef on its ability to counteract SERINC restriction and the clinical course of infection. HIV-1 Nef sequences were obtained from 123 participants of the Amsterdam Cohort Studies and showed multiple amino acid variations and mutations. Most of the primary Nef proteins showed increased activity to counteract SERINC3 and SERINC5 as compared to NL4-3 Nef. Several mutations in Nef were associated with either an increased or decreased infectivity of Bal26-pseudotyped HIV-1 produced in the presence of SERINC3 or SERINC5. The 8R, 157N and R178G Nef mutations were shown to have an effect on disease progression. Survival analysis showed an accelerated disease progression of individuals infected with HIV-1 carrying arginine or asparagine at position 8 or 157 in Nef, respectively, or the R178G Nef mutation. Here, we observed that naturally occurring mutations in Nef affect the ability of Nef to counteract SERINC3- and SERINC5-mediated inhibition of viral infectivity. The majority of these Nef mutations had no significant effect on HIV-1 pathogenesis and only the 8R, 157N and R178G mutations were associated with disease course.

scholarly journals Chronic corticosterone enhancement aggravates alpha-synuclein brain spreading pathology and substantia nigra neurodegeneration in mice

2018 ◽  
Author(s):  
Johannes Burtscher ◽  
Jean-Christophe Copin ◽  
João Rodrigues ◽  
Senthil K. Thangaraj ◽  
Anass Chiki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disease Progression ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Motor Symptom ◽  
Intracerebral Injection ◽  
Lewy Pathology ◽  
Physiological Adaptations ◽  
Corticosterone Treatment ◽  
The Impact

AbstractChronic stress and associated heightened glucocorticoid levels are risk factors for depression, a common non-motor symptom in Parkinson’s disease (PD). However, how heightened glucocorticoids influence PD neuropathology [alpha-synuclein (α-Syn) containing Lewy pathology and neurodegeneration] and disease progression is unclear. To address this knowledge gap, we investigated the impact of chronic corticosterone administration on α-Syn pathology, neurodegeneration, behavior and mitochondrial function in a mouse model of α-Syn pathology spreading after intracerebral injection of α-Syn preformed fibrils (PFFs). Our results demonstrate that heightened corticosterone aggravates neurodegeneration and α-Syn pathology spreading, intriguingly to specific brain regions, such as the entorhinal cortex. Corticosterone-treatment abolished distinct physiological adaptations after PFF-injection and induced differential physiological and behavioral consequences. Taken together, our work points to elevated glucocorticoids as a risk factor for the development of the neuropathological hallmarks of PD. Strategies aimed at reducing glucocorticoid levels might slow down pathology spreading and disease progression in synucleinopathy.

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