Assessing Effects of HIV Heterogeneity and Macrophage on the HIV Pathogenesis in HIV-Infected Individuals

Model of HIV pathogenesis in HIV-infected individuals under very general conditions. In this model, we have considered five different types of CD4(+)T cells, two different types of HIV (M-tropic versus T-tropic) as well as infected and un-infected macrophage. This is a 9-dimensional stochastic process. For this process, we have developed stochastic differential equations for different types of cells. By using these stochastic equations, we have generated some Monte Carlo data to study the stochastic behavior of the HIV pathogenesis and the HIV progression.Through Monte Carlo studies, we have revealed an acute infection stage in the early stage of the HIV infection and have confirmed the basic role played by lymph nodes and some long-lived cells such as macrophage in serving as reservoirs of HIV to escape elimination by the immune system during the long asymptomatic stage of HIV infection. The Monte Carlo results have shown that the HIV heterogeneity and diversity may be a major factor to determine the time period since infection for uninfected T cells to drop to below 200/mm3of blood. The numerical results have also confirmed our previous findings (see [1]) which concluded that the probability distributions of T cells and free HIV can be classified into three periods over time: The latent period, the transition period and the pseudo-steady period.

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Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection

Blood ◽

10.1182/blood-2012-04-422550 ◽

2012 ◽

Vol 120 (17) ◽

pp. 3466-3477 ◽

Cited By ~ 46

Author(s):

Lydie Trautmann ◽

Florentin-Martial Mbitikon-Kobo ◽

Jean-Philippe Goulet ◽

Yoav Peretz ◽

Yu Shi ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Hiv Infection ◽

Cd8 T Cells ◽

Primary Infection ◽

Acute Infection ◽

T Cell Response ◽

Viral Control ◽

Metabolic State ◽

Host Virus Interactions

AbstractImmediate-early host-virus interactions that occur during the first weeks after HIV infection have a major impact on disease progression. The mechanisms underlying the failure of HIV-specific CD8 T-cell response to persist and control viral replication early in infection are yet to be characterized. In this study, we performed a thorough phenotypic, gene expression and functional analysis to compare HIV-specific CD8 T cells in acutely and chronically infected subjects. We showed that HIV-specific CD8 T cells in primary infection can be distinguished by their metabolic state, rate of proliferation, and susceptibility to apoptosis. HIV-specific CD8 T cells in acute/early HIV infection secreted less IFN-γ but were more cytotoxic than their counterparts in chronic infection. Importantly, we showed that the levels of IL-7R expression and the capacity of HIV-specific CD8 T cells to secrete IL-2 on antigenic restimulation during primary infection were inversely correlated with the viral set-point. Altogether, these data suggest an altered metabolic state of HIV-specific CD8 T cells in primary infection resulting from hyperproliferation and stress induced signals, demonstrate the discordant function of HIV-specific CD8 T cells during early/acute infection, and highlight the importance of T-cell maintenance for viral control.

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Impact of Biological Sex on Immune Activation and Frequency of the Latent HIV Reservoir During Suppressive Antiretroviral Therapy

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa298 ◽

2020 ◽

Vol 222 (11) ◽

pp. 1843-1852 ◽

Cited By ~ 3

Author(s):

Shane D Falcinelli ◽

Bonnie E Shook-Sa ◽

Morgan G Dewey ◽

Sumati Sridhar ◽

Jenna Read ◽

...

Keyword(s):

T Cells ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

Immune Activation ◽

Cd4 T Cells ◽

Acute Infection ◽

Interferon Response ◽

Suppressive Therapy ◽

Hiv Reservoir ◽

Latent Hiv

Abstract Background Persistent HIV infection of long-lived resting CD4 T cells, despite antiretroviral therapy (ART), remains a barrier to HIV cure. Women have a more robust type 1 interferon response during HIV infection relative to men, contributing to lower initial plasma viremia. As lower viremia during acute infection is associated with reduced frequency of latent HIV infection, we hypothesized that women on ART would have a lower frequency of latent HIV compared to men. Methods ART-suppressed, HIV seropositive women (n = 22) were matched 1:1 to 22 of 39 ART-suppressed men. We also compared the 22 women to all 39 men, adjusting for age and race as covariates. We measured the frequency of latent HIV using the quantitative viral outgrowth assay, the intact proviral DNA assay, and total HIV gag DNA. We also performed activation/exhaustion immunophenotyping on peripheral blood mononuclear cells and quantified interferon-stimulated gene (ISG) expression in CD4 T cells. Results We did not observe evident sex differences in the frequency of persistent HIV in resting CD4 T cells. Immunophenotyping and CD4 T-cell ISG expression analysis revealed marginal differences across the sexes. Conclusions Differences in HIV reservoir frequency and immune activation appear to be small across sexes during long-term suppressive therapy.

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Elevated levels and Clinical Association of Serum Cytokines in Untreated HIV-1 Infection

10.21203/rs.3.rs-534115/v1 ◽

2021 ◽

Author(s):

Na Zhang ◽

Chang-Xin Yan ◽

Shuang-Mei Yu ◽

Xiao-Xiong Wang ◽

Lei Teng ◽

...

Keyword(s):

T Cells ◽

Immune System ◽

T Cell ◽

Hiv Infection ◽

Early Stage ◽

Serum Levels ◽

Underlying Mechanism ◽

Cell Counts ◽

Aids Progression ◽

Hiv 1

Abstract Background Human immunodeficiency virus type 1 (HIV-1) infection disturbs the balance of CD4+ T cells and monocytes in the immune system. In the early stage of infection, the virus stimulates the activation and proliferation of immune cells, induces the release of cytokines, destroys CD4+ T cells, and accelerates HIV-1 replication and AIDS progression. It is essential to explore cytokine changes after HIV-1 infection and further understand the underlying mechanism of HIV infection. Methods In this study, we enrolled 38 HIV-infected subjects and 30 healthy subjects. We measured and compared CD4+ T cell counts and the serum cytokine levels in different groups. Results Our results showed significantly higher serum levels of IL-1β, IL-2, IL-4, IL-7, IL-10, IL-17, IFN-γ, and TNF-α in HIV-infected patients. Higher levels of IL-6 and IL-17 were observed in the < 200/mL CD4+ T cell count group, and higher levels of IL-2 were observed in the CCR5-tropic HIV strain group. Conclusion In conclusion, we found that HIV infection-induced activation of the immune system and cytokines could predict the severity of HIV disease and regulate HIV infection and replication differently depending on the type of virus strain.

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PHASE TRANSITION IN THREE-DIMENSIONAL ISING SYSTEMS WITH QUENCHED NON-MAGNETIC IMPURITIES: A REVIEW OF MONTE CARLO STUDIES

International Journal of Modern Physics B ◽

10.1142/s0217979289000889 ◽

1989 ◽

Vol 03 (09) ◽

pp. 1343-1376 ◽

Cited By ~ 13

Author(s):

P. BRAUN ◽

U. STAADEN ◽

T. HOLEY ◽

M. FÄHNLE

Keyword(s):

Phase Transition ◽

Monte Carlo ◽

Order Parameter ◽

Three Dimensional ◽

Magnetic Impurities ◽

Monte Carlo Data ◽

Multispin Coding ◽

Pure System ◽

Monte Carlo Studies ◽

The One

A review is given of Monte Carlo simulations for the phase transition in simple cubic Ising ferro-, ferri-, and antiferromagnets with quenched non-magnetic impurities of concentration x. Special emphasis is given on the description of a fully vectorized multispin coding program and on the problems related to the analysis of the Monte Carlo data. The following three subjects are discussed: 1) For ferro- and antiferromagnets, the critical behaviour of the order parameter is different from the one of the corresponding pure system, in agreement with the prediction of the Harris criterion. The possibly effective exponent β depends on x, whereas for ferrimagnets no such concentration dependence is revealed by the present study for x=0, 0.1, and 0.2.2) For strongly diluted systems, there is a maximum for the Kouvel-Fisher exponent γ(T) of the order-parameter susceptibility outside the critical regime, in accordance with the predictions of the correlated molecular field theory. 3) For the diluted antiferromagnet (x=0.5), a cusp emerges at T c for the uniform susceptibility, in agreement with the theory of Fishman and Aharony.

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Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection

Journal of Virology ◽

10.1128/jvi.02785-15 ◽

2016 ◽

Vol 90 (8) ◽

pp. 4005-4016 ◽

Cited By ~ 12

Author(s):

Michael A. Eller ◽

Nilu Goonetilleke ◽

Boonrat Tassaneetrithep ◽

Leigh Anne Eller ◽

Margaret C. Costanzo ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Hiv Infection ◽

Cell Population ◽

Acute Infection ◽

T Cell Responses ◽

Hiv Replication ◽

Acute Hiv Infection ◽

Cell Responses ◽

Acute Hiv

ABSTRACTAttrition within the CD4+T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8+T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8+T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38+CD27−CD8+T cells characterized by the low expression of the CD8 receptor (CD8dim). Interestingly, while high frequencies of HIV-specific CD8+T cell responses occur within the CD38+CD27−CD8dimT cell population, the minority populations of CD8brightT cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8dimT cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8dimT cells, and the size of this population inversely correlates with the acute loss of CD4+T cells. These data indicate, for the first time, that early CD4+T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8dimT cell population less efficient in controlling HIV viremia.IMPORTANCEA distinct population of activated CD8+T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8+T cell dysfunction during acute infection.

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