scholarly journals Reduction of HIV-1 Reservoir Size and Diversity After 1 Year of cART Among Brazilian Individuals Starting Treatment During Early Stages of Acute Infection

2019 ◽  
Vol 10 ◽  
Author(s):  
Thaysse Ferreira Leite ◽  
Edson Delatorre ◽  
Fernanda Heloise Côrtes ◽  
Ana Cristina Garcia Ferreira ◽  
Sandra Wagner Cardoso ◽  
...  
Keyword(s):  
Acute Infection ◽  
Early Stages ◽  
Hiv 1

scholarly journals HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Brennan S. Dirk ◽  
Emily N. Pawlak ◽  
Aaron L. Johnson ◽  
Logan R. Van Nynatten ◽  
Rajesh A. Jacob ◽  
...  
Keyword(s):  
Mhc I ◽  
Early Stages ◽  
Hiv 1

Effect of antiretroviral therapy on HIV-1 genetic evolution during acute infection

2011 ◽  
Vol 22 (3) ◽  
pp. 146-150 ◽  
Author(s):  
A Chamberland ◽  
M Sylla ◽  
M R Boulassel ◽  
J-G Baril ◽  
P Côté ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Acute Infection ◽  
Genetic Evolution ◽  
Hiv 1

scholarly journals Comprehensive Analysis of Human Immunodeficiency Virus Type 1-Specific CD4 Responses Reveals Marked Immunodominance of gag and nef and the Presence of Broadly Recognized Peptides

2004 ◽  
Vol 78 (9) ◽  
pp. 4463-4477 ◽  
Author(s):  
Daniel E. Kaufmann ◽  
Paul M. Bailey ◽  
John Sidney ◽  
Bradford Wagner ◽  
Philip J. Norris ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Consensus Sequence ◽  
Acute Infection ◽  
Hla Dr ◽  
Immunodeficiency Virus ◽  
Total Magnitude ◽  
Hiv 1

ABSTRACT Increasing evidence suggests that human immunodeficiency virus type 1 (HIV-1)-specific CD4 T-cell responses contribute to effective immune control of HIV-1 infection. However, the breadths and specificities of these responses have not been defined. We screened fresh CD8-depleted peripheral blood mononuclear cells (PBMC) from 36 subjects at different stages of HIV-1 infection for virus-specific CD4 responses by gamma interferon enzyme-linked immunospot assay, using 410 overlapping peptides spanning all HIV-1 proteins (based on the clade B consensus sequence). HIV-1-specific CD4 responses were identified in 30 of the 36 individuals studied, with the strongest and broadest responses detected in persons treated in acute infection who underwent treatment interruption. In individuals with identified responses, the total number of recognized HIV-1 peptides ranged from 1 to 36 (median, 7) and the total magnitude of responses ranged from 80 to >14,600 (median, 990) spot-forming cells/106 CD8-depleted PBMC. Neither the total magnitude nor the number of responses correlated with viremia. The most frequent and robust responses were directed against epitopes within the Gag and Nef proteins. Peptides targeted by ≥25% of individuals were then tested for binding to a panel of common HLA-DR molecules. All bound broadly to at least four of the eight alleles tested, and two bound to all of the HLA-DR molecules studied. Fine mapping and HLA restriction of the responses against four of these peptides showed a combination of clustering of epitopes and promiscuous presentation of the same epitopes by different HLA class II alleles. These findings have implications for the design of immunotherapeutic strategies and for testing candidate HIV vaccines.

scholarly journals Frequencies of circulating Th1-biased T follicular helper cells in acute HIV-1 infection correlate with the development of HIV-specific antibody responses and lower set point viral load

2018 ◽  
Author(s):  
Omolara Baiyegunhi ◽  
Bongiwe Ndlovu ◽  
Funsho Ogunshola ◽  
Nasreen Ismail ◽  
Bruce D. Walker ◽  
...  
Keyword(s):  
Viral Load ◽  
Neutralizing Antibodies ◽  
Acute Infection ◽  
Antibody Responses ◽  
Set Point ◽  
Follicular Helper ◽  
Clade C ◽  
Acute Hiv ◽  
Anti Hiv ◽  
Hiv 1

AbstractDespite decades of focused research, the field has yet to develop a prophylactic vaccine. In the RV144 vaccine trial, non-neutralizing antibody responses were identified as a correlate for prevention of HIV acquisition. However, factors that predict the development of such antibodies are not fully elucidated. We sought to define the contribution of circulating T follicular helper (cTfh) cell subsets to the development of non-neutralizing antibodies in HIV-1 clade C infection. Study participants were recruited from an acute HIV-1 clade C infection cohort. Plasma anti-gp41, -gp120, -p24 and -p17 antibodies were screened using a customized multivariate Luminex assay. Phenotypic and functional characterization of cTfh were performed using HLA class II tetramers and intracellular cytokine staining. In this study, we found that acute HIV-1 clade C infection skewed differentiation of functional cTfh subsets towards increased Tfh1 (p=0.02) and Tfh2 (p<0.0001) subsets, with a concomitant decrease in overall Tfh1-17 (that shares both Tfh1 and Tfh17 properties) (p=0.01) and Tfh17 subsets (p<0.0001) compared to HIV negative subjects. Interestingly, the frequencies of Tfh1 during acute infection (5.0-8.0 weeks post-infection) correlated negatively with set point viral load (p=0.03, r=-60) and were predictive of p24-specific plasma IgG titers at one year of infection (p=0.003, r=0.85). Taken together, our results suggest that circulating the Tfh1 subset plays an important role in the development of anti-HIV antibody responses and contributes to HIV suppression during acute HIV-1 infection. These results have implications for vaccine studies aimed at inducing long lasting anti-HIV antibody responses.ImportanceThe HIV epidemic in southern Africa accounts for almost half of the global HIV burden with HIV-1 clade C being the predominant strain. It is therefore important to define immune correlates of clade C HIV control that might have implications for vaccine design in this region. T follicular helper (Tfh) cells are critical for the development of HIV-specific antibody responses and could play a role in viral control. Here we showed that the early induction of circulating Tfh1 cells during acute infection correlated positively with the magnitude of p24-specific IgG and was associated with lower set point viral load. This study highlights a key Tfh cell subset that could limit HIV replication by enhancing antibody generation. This study underscores the importance of circulating Tfh cells in promoting non-neutralizing antibodies during HIV-1 infection.

scholarly journals Oligomerization Requirements for MX2-Mediated Suppression of HIV-1 Infection

2015 ◽  
Vol 90 (1) ◽  
pp. 22-32 ◽  
Author(s):  
Matthew D. J. Dicks ◽  
Caroline Goujon ◽  
Darja Pollpeter ◽  
Gilberto Betancor ◽  
Luis Apolonia ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Structure Function ◽  
Influenza A ◽  
Acute Infection ◽  
Higher Order ◽  
Nuclear Accumulation ◽  
Antiviral Function ◽  
Ring Structures ◽  
Hiv 1

ABSTRACTHuman myxovirus resistance 2 (MX2/MXB) is an interferon-stimulated gene (ISG) and was recently identified as a late postentry suppressor of human immunodeficiency virus type 1 (HIV-1) infection, inhibiting the nuclear accumulation of viral cDNAs. Although the HIV-1 capsid (CA) protein is believed to be the viral determinant of MX2-mediated inhibition, the precise mechanism of antiviral action remains unclear. The MX family of dynamin-like GTPases also includes MX1/MXA, a well-studied inhibitor of a range of RNA and DNA viruses, including influenza A virus (FLUAV) and hepatitis B virus but not retroviruses. MX1 and MX2 are closely related and share similar domain architectures and structures. However, MX2 possesses an extended N terminus that is essential for antiviral function and confers anti-HIV-1 activity on MX1 [MX1(NMX2)]. Higher-order oligomerization is required for the antiviral activity of MX1 against FLUAV, with current models proposing that MX1 forms ring structures that constrict around viral nucleoprotein complexes. Here, we performed structure-function studies to investigate the requirements for oligomerization of both MX2 and chimeric MX1(NMX2) for the inhibition of HIV-1 infection. The oligomerization state of mutated proteins with amino acid substitutions at multiple putative oligomerization interfaces was assessed using a combination of covalent cross-linking and coimmunoprecipitation. We show that while monomeric MX2 and MX1(NMX2) mutants are not antiviral, higher-order oligomerization does not appear to be required for full antiviral activity of either protein. We propose that lower-order oligomerization of MX2 is sufficient for the effective inhibition of HIV-1.IMPORTANCEInterferon plays an important role in the control of virus replication during acute infectionin vivo. Recently, cultured cell experiments identified human MX2 as a key effector in the interferon-mediated postentry block to HIV-1 infection. MX2 is a member of a family of large dynamin-like GTPases that includes MX1/MXA, a closely related interferon-inducible inhibitor of several viruses, including FLUAV, but not HIV-1. MX GTPases form higher-order oligomeric structures, and the oligomerization of MX1 is required for inhibitory activity against many of its viral targets. Through structure-function studies, we report that monomeric mutants of MX2 do not inhibit HIV-1. However, in contrast to MX1, oligomerization beyond dimer assembly does not seem to be required for the antiviral activity of MX2, implying that fundamental differences exist between the antiviral mechanisms employed by these closely related proteins.

scholarly journals Better Viral Control despite Higher CD4+ T Cell Activation during Acute HIV-1 Infection in Zambian Women Is Linked to the Sex Hormone Estradiol

2020 ◽  
Vol 94 (16) ◽  
Author(s):  
Elina El-Badry ◽  
Gladys Macharia ◽  
Daniel Claiborne ◽  
Kelsie Brooks ◽  
Darío A. Dilernia ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Acute Infection ◽  
Chronic Phase ◽  
Cell Loss ◽  
Viral Control ◽  
Acute Hiv ◽  
17Β Estradiol ◽  
Hiv 1

ABSTRACT The influence of biological sex on disease progression in HIV-1-infected individuals has been focused on the chronic stage of infection, but little is known about how sex differences influence acute HIV-1 infection. We observed profound differences in viral load and CD4+ T cell activation from the earliest time points in men and women in a Zambian heterosexual acute infection cohort. Women exhibited a >2-fold higher rate of CD4+ T cell loss despite significantly lower viral loads (VL) than men. The importance of studying acute infection was highlighted by the observation that very early in infection, women exhibited significantly higher levels of CD4+ T cell activation, a difference that was lost over the first 3 years of infection as activation in men increased. In women, activation of CD4+ T cells in the acute phase was significantly correlated with plasma levels of 17β-estradiol (E2). However, unlike in men, higher CD4+ T cell activation in women was not associated with higher VL. In contrast, a higher E2 level in early infection was associated with lower early and set-point VL in women. We attribute this to an inhibitory effect of estradiol on virus replication, which we were able to observe with relevant transmitted/founder viruses in vitro. Thus, estradiol plays a key role in defining major differences between men and women during early HIV-1 infection by contributing to both viral control and CD4+ T cell loss, an effect that extends into the chronic phase of the disease. IMPORTANCE Previous studies have identified sex-specific differences during chronic HIV-1 infection, but little is known about sex differences in the acute phase, or how disparities in the initial response to the virus may affect disease. We demonstrate that restriction of viral load in women begins during acute infection and is maintained into chronic infection. Despite this, women exhibit more rapid CD4+ T cell loss than men. These profound differences are influenced by 17β-estradiol, which contributes both to T cell activation and to reduced viral replication. Thus, we conclude that estradiol plays a key role in shaping responses to early HIV-1 infection that influence the chronic phase of disease.

scholarly journals Expansion of activated T lymphocytes (CD3+HLA/DR+) detectable in early stages of HIV-1 infection

1990 ◽  
Vol 68 (8) ◽  
pp. 393-396 ◽  
Author(s):  
J. R. Bogner ◽  
A. Matuschke ◽  
B. Heinrich ◽  
M. A. Schreiber ◽  
C. Nerl ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Early Stages ◽  
Hla Dr ◽  
Activated T Lymphocytes ◽  
Hiv 1

scholarly journals Characterization of New HIV Infections among Adults ≥45 Years—New York City, North Carolina, San Francisco, 2011–2013

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S15-S15
Author(s):  
Mary Evans ◽  
Anne Patala ◽  
Ellsworth Campbell ◽  
Emily Westheimer ◽  
Cynthia L Gay ◽  
...  
Keyword(s):  
Older Adults ◽  
Hiv Prevention ◽  
Hiv Infection ◽  
San Francisco ◽  
Acute Infection ◽  
Study Participant ◽  
Rapid Test ◽  
Bivariate Analysis ◽  
Similar Frequency ◽  
Hiv 1

Abstract Background While HIV prevention activities are often focused on younger people, older people can also be at risk for HIV infection. We aimed to characterize HIV transmission in older adults. Methods The STOP study was a multi-site prospective study of persons with acute HIV infection (AHI) from 2011 to 2013. Older adults were defined as ≥45 years and younger persons were 13–44 years. AHI was defined by a negative rapid test but a reactive antigen/antibody or HIV RNA test. We performed bivariate analysis using Pearson’s chi-square and odds ratios to examine associations between older age and transmission characteristics. Among persons with HIV-1 polymerase (pol) sequences, transmission linkages were inferred when the genetic distance between sequences was &lt;1.5% and did not indicate directionality of transmission. Results Among 86,836 participants (median age, 29 years; 75.0% male; 51.8% MSM), HIV infection was diagnosed in 176 (1.46%) of 12,036 older adults compared with 1,150 (1.53%) of 74,800 younger people (P = 0.56). Among HIV-infected persons, AHI was diagnosed in similar proportions of older and younger people (13.1% vs. 12.6%; P = 0.86). Among HIV-infected persons who participated in partner notification (n = 1,326), older adults were less likely to report meeting a sex partner online (11.3% vs. 26.9%; OR 0.52, 95% CI = 0.35–0.78) and were less likely to name ≥2 sex partners (31.5% vs. 46.8%; OR = 0.28, 95% CI = 0.15–0.53) compared with younger people. Among HIV-infected persons with HIV-1 pol sequences (n = 537), similar proportions of older and younger people had viruses that genetically linked with another study participant (15.9% vs. 23.5%; OR 0.62, 95% CI 0.31–1.22) (Figure). Conclusion In this study, older adults had a similar frequency of newly diagnosed HIV infection, acute infection, and genetic linkage compared with younger people, suggesting that increased HIV prevention efforts may be needed in this population. Disclosures All authors: No reported disclosures.

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