Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects

CD4+ CCR6+ T cells are highly susceptible to HIV infection, and a high cytokine producing CCR6+ T cell subset is selectively lost during HIV infection. The CCR6 chemokine MIP-3α (CCL20) is produced at sites of infection in SIV animal models. Recently, we have shown that MIP-3α inhibits HIV replication. This inhibition of HIV infection is mediated by CCR6 signaling and eventuates in increased APOBEC3G expression. Since there are no existing reports on the role of MIP-3α in health or disease, we studied its production by PBMCs from HIV-seronegative and HIV+ subjects. We evaluated the ability of PBMCs to produce MIP-3α in response to antigen stimulation using cells obtained from two groups: one composed of HIV-seronegative subjects (n = 16) and the other composed of HIV+ subjects (n = 58), some asymptomatic and some with clinically defined AIDS. Antigens included fragment C of the tetanus toxin, Candida albicans, whole-inactivated HIV, and HIV p24. MIP-3α was detected by ELISA in tissue culture supernatants of antigen-stimulated PBMCs. MIP-3α production by antigen-stimulated PBMCs was readily measured for HIV-negative subjects and for HIV-seropositive asymptomatic subjects, but not for patients with AIDS. These results suggest that subversion of the MIP-3α-CCR6 axis by HIV during the course of infection contributes to the loss of immune function that eventually leads to AIDS.

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HLA-E Up-Regulation Induced by HIV Infection May Directly Contribute to CD94-Mediated Impairment of NK Cells

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200501800209 ◽

2005 ◽

Vol 18 (2) ◽

pp. 269-276 ◽

Cited By ~ 26

Author(s):

F. Martini ◽

C. Agrati ◽

G. D'Offizi ◽

F. Poccia

Keyword(s):

T Cells ◽

Hiv Infection ◽

Nk Cells ◽

Cd4 T Cells ◽

Nk Cell ◽

Treatment Interruption ◽

Cell Number ◽

Hiv Replication

Alterations in NK cell numbers and function have been repeatedly shown during HIV infection. In this study, NK cell number and MHC class I expression on CD4+ T cells were studied in HIV patients at different stages of disease progression. An increased expression of HLA-E was seen on CD4+ T cells. In parallel, a reduced number of CD94+ NK cells was observed in advanced disease stages. Moreover, a decline in CD94 expression on NK cells was observed at the HIV replication peak in patients undergoing antiretroviral treatment interruption, suggesting a role of viral replication on NK cells alterations. In vitro HIV infection induced a rapid down-regulation of HLA-A,B,C expression, paralleled by an increased expression of HLA-E surface molecules, the formal ligands of CD94 NK receptors. HIV-infected HLA-E expressing cells were able to inhibit NK cell cytotoxicity through HLA-E expression, since cytotoxicity was restored by antibody masking experiments. These data indicate that the CD94/HLA-E interaction may contribute to NK cell dysfunction in HIV infection, suggesting a role of HIV replication in this process.

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Localization of Human Immunodeficiency Virus Core Antigen in Term Human Placentas

PEDIATRICS ◽

10.1542/peds.89.2.207 ◽

1992 ◽

Vol 89 (2) ◽

pp. 207-209

Author(s):

Carl F. T. Mattern ◽

Karen Murray ◽

Allison Jensen ◽

Homayoon Farzadegan ◽

Jenny Pang ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hiv Infection ◽

Mononuclear Cells ◽

Morphological Characteristics ◽

Core Antigen ◽

Hiv Replication ◽

Immunodeficiency Virus ◽

Maternal Hiv ◽

Maternal Hiv Infection ◽

Hiv Seropositive

Evidence of human immunodeficiency virus (HIV) replication was sought in human placentas obtained at term from pregnancies complicated by maternal HIV infection. Placentas were obtained from the pregnancies of 19 HIV-seropositive women, 4 women who were seronegative, and 4 untested women with no risk factors for HIV infection. These placentas were each examined by immunoperoxidase immunocytochemistry using monoclonal anti-p24/55 antibodies. In addition, minced placental tissue from 11 of the seropositive pregnancies and the 3 seronegative pregnancies were co-cultivated with stimulated human peripheral blood mononuclear cells. The clinical status of the infants born to the HIV-seropositive women was assessed when the infants were 8 to 28 months of age. P24/55 antigen was detected in 5 of the 19 placentas of the HIV-seropositive pregnancies and in none of the 8 placentas of seronegative or low-risk pregnancies. This HIV core viral antigen was located exclusively in the cytoplasm of villous cells with morphological characteristics of macrophages. The HIV antigen-containing cells were very sparsely distributed. Staining of the trophoblast was not observed in any placental specimen. Human immunodeficiency virus was isolated in culture from 3 of the 11 placentas from seropositive pregnancies. Clinical follow-up has not revealed a relationship between infection of the infant and either p24/55 antigen identification or isolation of virus from the placenta. Virological and histological evidence of HIV replication is found in approximately one fourth of placentas obtained at term from pregnancies complicated by maternal HIV infection. Replicating virus appears localized to sparse macrophages located within the chorionic villi, but specifically not within the trophoblastic layer. It is unlikely that identification of HIV in the placenta either by culture or by immunocytochemistry will predict infection of infants born to seropositive women.

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HIV reprograms host m6Am RNA methylome by viral Vpr protein-mediated degradation of PCIF1

Nature Communications ◽

10.1038/s41467-021-25683-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Qiong Zhang ◽

Yuqi Kang ◽

Shaobo Wang ◽

Gwendolyn Michelle Gonzalez ◽

Wanyu Li ◽

...

Keyword(s):

T Cells ◽

Transcription Factor ◽

Hiv Infection ◽

Viral Protein ◽

Rna Modification ◽

Hiv Replication ◽

Dramatic Decrease ◽

Host Interactions ◽

Cellular Mrnas

AbstractN6,2′-O-dimethyladenosine (m6Am) is an abundant RNA modification located adjacent to the 5′-end of the mRNA 7-methylguanosine (m7G) cap structure. m6A methylation on 2′-O-methylated A at the 5′-ends of mRNAs is catalyzed by the methyltransferase Phosphorylated CTD Interacting Factor 1 (PCIF1). The role of m6Am and the function of PCIF1 in regulating host–pathogens interactions are unknown. Here, we investigate the dynamics and reprogramming of the host m6Am RNA methylome during HIV infection. We show that HIV infection induces a dramatic decrease in m6Am of cellular mRNAs. By using PCIF1 depleted T cells, we identify 2237 m6Am genes and 854 are affected by HIV infection. Strikingly, we find that PCIF1 methyltransferase function restricts HIV replication. Further mechanism studies show that HIV viral protein R (Vpr) interacts with PCIF1 and induces PCIF1 ubiquitination and degradation. Among the m6Am genes, we find that PCIF1 inhibits HIV infection by enhancing a transcription factor ETS1 (ETS Proto-Oncogene 1, transcription factor) stability that binds HIV promoter to regulate viral transcription. Altogether, our study discovers the role of PCIF1 in HIV–host interactions, identifies m6Am modified genes in T cells which are affected by viral infection, and reveals how HIV regulates host RNA epitranscriptomics through PCIF1 degradation.

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Factors influencing tymic function in 55 patients with lymphomas: Candidates to autologous stem cell transplantation (ASCT)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18512 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18512-18512 ◽

Cited By ~ 1

Author(s):

C. Simonelli ◽

C. Pratesi ◽

S. Zanussi ◽

R. Talamini ◽

M. Rupolo ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

De Novo ◽

Good Control ◽

Cell Receptor ◽

Hiv Positive ◽

First Line ◽

Hiv Replication ◽

Excision Circles ◽

Hiv Negative

18512 Background: Signal joint T cell receptor excision circles (sjTRECs) have been reported to be a clinical marker to evaluate the tymic reservoir after immunosuppression treatments. Methods: We studied the sjTRECs levels in a mono-institutional series of a cohort of 26 HIV-positive and 29 HIV-negative pts with relapsed or refractory lymphomas, candidates to ASCT, considering important biological and clinical characteristics, virological parameters and immunological settings including age, type of lymphoma, number of first line CT cycles, time from the end of first line chemotherapy to the enrolment (TECT), HIV infection and T subpopulations. Results: The overall study subjects, showed lower sjTRECs levels than healthy donors (p<0.01), but no differences in the sjTRECs content were seen between HIV-negative and HIV-positive pts (536 vs. 401 TRECs/106 PBMCs, respectively) as well as in the T cell naive count. We found a significant correlation between the sjTRECs decay and the increase of age (r=-0.32, p=0.02), CD4 and CD8 naive cell count and the sjTRECs level; on the contrary we did not observe any significant correlation between CT cycles number TECT, lymphoma type in both subgroups. HIV-positive viremic pts showed significant lower level of sjTRECs level than averimic pts. Conclusions: Our analyses suggest that de novo T cell generation is partially maintained in lymphoma pts’ candidates to ASCT and could contribute to restore the immune function after transplantation. Chemotherapeutic treatments seem to induce a similar influence on thymic output despite their intensity and, surprisingly, HIV infection is not a detrimental factor on thymic reservoir at the time of lymphoma relapse, and a good control of HIV replication seems to preserve thymic reservoir. No significant financial relationships to disclose.

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Interaction between Endogenous Bacterial Flora and Latent HIV Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00766-12 ◽

2013 ◽

Vol 20 (6) ◽

pp. 773-779 ◽

Cited By ~ 3

Author(s):

Ann Florence B. Victoriano ◽

Kenichi Imai ◽

Takashi Okamoto

Keyword(s):

Hiv Infection ◽

Opportunistic Infections ◽

Bacterial Flora ◽

Anaerobic Bacteria ◽

Hiv Replication ◽

Latently Infected ◽

Potential Link ◽

Infected Cells ◽

Latent Hiv

ABSTRACTHuman commensal bacteria do not normally cause any diseases. However, in certain pathological conditions, they exhibit a number of curious behaviors. In HIV infection, these bacteria exhibit bidirectional relationships: whereas they cause opportunistic infections based on immunological deterioration, they also augment HIV replication, in particular, viral replication from latently infected cells, which is attributable to the effect of butyric acid produced by certain anaerobic bacteria by modifying the state of chromatin. Here, we review recent evidence supporting the contributory role of such endogenous microbes in disrupting HIV latency and its potential link to the clinical progression of AIDS.

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Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa375 ◽

2020 ◽

Author(s):

Eva Poveda ◽

Andrés Tabernilla ◽

Wendy Fitzgerald ◽

Ángel Salgado-Barreira ◽

Marta Grandal ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hiv Infection ◽

Elite Controllers ◽

Hiv Replication ◽

Mitochondrial Density ◽

Cellular Origin ◽

Immunodeficiency Virus ◽

Virologic Control ◽

Polymerase Chain

Abstract Background The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. Methods Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. Results Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. Conclusions A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.

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CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation

Clinical and Developmental Immunology ◽

10.1080/10446670310001598519 ◽

2003 ◽

Vol 10 (1) ◽

pp. 13-17 ◽

Cited By ~ 19

Author(s):

Vanessa Ubaldi ◽

Lucia Gatta ◽

Luigia Pace ◽

Gino Doria ◽

Claudio Pioli

Keyword(s):

Transcriptional Activation ◽

Cell Subset ◽

Th2 Cells ◽

T Helper ◽

Th1 Cell ◽

Th Cell ◽

Ifn Γ ◽

Culture Supernatants ◽

Th1 And Th2

CTLA-4 deficient mice show severe lymphoproliferative disorders with T helper sub-population skewed toward the Th2 phenotype. In the present work, we investigated the role of CTLA-4 in T helper cell subset differentiation. Naïve CD4+cells were stimulated with anti-CD3 and anti-CD28 mAbs in the presence of either IL-12 or IL-4 to induce polarisation to Th1 or Th2 cells, respectively. Under these two polarising conditions cells express comparable levels of CTLA-4. CTLA-4 was stimulated by plastic-bound mAb. The frequency of IFN-γ- and IL-4-producing cells were estimated by FACS analysis. In parallel cultures, polarised Th1 and Th2 cells were re-stimulated with anti-CD3 and anti-CD28 mAbs for 48 h and their culture supernatants analysed by ELISA. Results show that CTLA-4 engagement during differentiation inhibits polarisation of naïve CD4+cells to the Th2 but not the Th1 cell subset. At variance, once cells are polarised, CTLA-4 engagement inhibits cytokine production in both effector Th2 and Th1 cells. Altogether these data indicate that CTLA-4 may interfere not only in the signalling involved in acute transcriptional activation of both Th1 and Th2 cells but also in the development of one of the Th cell subsets.

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Liver disease, HIV and aging

Sexual Health ◽

10.1071/sh10163 ◽

2011 ◽

Vol 8 (4) ◽

pp. 512 ◽

Cited By ~ 10

Author(s):

Oluwaseun Falade-Nwulia ◽

Chloe L. Thio

Keyword(s):

Liver Disease ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

Highly Active Antiretroviral Therapy ◽

Future Research ◽

Hiv Replication ◽

Highly Active ◽

Living With Hiv ◽

The Impact ◽

Hiv Negative

The life expectancy of HIV-infected patients has increased due to the efficacy of highly active antiretroviral therapy (HAART) in controlling HIV replication; thus, the population living with HIV infection is steadily aging. Liver-related morbidity and mortality has emerged as a leading problem in HIV-infected patients. Since aging, HIV infection and HAART all affect the liver, understanding the impact of the combination of these factors on liver disease is crucial for optimisation of care in the aging HIV-infected population. This review will focus on the current understanding of liver disease in older (>50 years old) HIV-negative individuals and in HIV-infected individuals. Areas for future research in the area of HIV, liver disease and aging will also be discussed.

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Increased Levels of Macrophage Inflammatory Proteins Result in Resistance to R5-Tropic HIV-1 in a Subset of Elite Controllers

Journal of Virology ◽

10.1128/jvi.00118-15 ◽

2015 ◽

Vol 89 (10) ◽

pp. 5502-5514 ◽

Cited By ~ 24

Author(s):

Wendy E. Walker ◽

Sebastian Kurscheid ◽

Samit Joshi ◽

Charlie A. Lopez ◽

Gerald Goh ◽

...

Keyword(s):

T Cells ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

Viral Entry ◽

Natural Resistance ◽

Elite Controllers ◽

Hiv Replication ◽

Inflammatory Protein ◽

Genes Encoding ◽

Hiv Seropositive

ABSTRACTElite controllers (ECs) are a rare group of HIV seropositive individuals who are able to control viral replication without antiretroviral therapy. The mechanisms responsible for this phenotype, however, have not been fully elucidated. In this study, we examined CD4+T cell resistance to HIV in a cohort of elite controllers and explored transcriptional signatures associated with cellular resistance. We demonstrate that a subgroup of elite controllers possess CD4+T cells that are specifically resistant to R5-tropic HIV while remaining fully susceptible to X4-tropic and vesicular stomatitis virus G (VSV-G)-pseudotyped viruses. Transcriptome analysis revealed 17 genes that were differentially regulated in resistant elite controllers relative to healthy controls. Notably, the genes encoding macrophage inflammatory protein 1α (MIP-1α),CCL3andCCL3L1, were found to be upregulated. The MIP-1α, MIP-1β, and RANTES chemokines are natural ligands of CCR5 and are known to interfere with HIV replication. For three elite controllers, we observed increased production of MIP-1α and/or MIP-1β at the protein level. The supernatant from resistant EC cells contained MIP-1α and MIP-1β and was sufficient to confer R5-tropic resistance to susceptible CD4+T cells. Additionally, this effect was reversed by using inhibitory anti-MIP antibodies. These results suggest that the T cells of these particular elite controllers may be naturally resistant to HIV infection by blocking R5-tropic viral entry.IMPORTANCEHIV is a pandemic health problem, and the majority of seropositive individuals will eventually progress to AIDS unless antiretroviral therapy (ART) is administered. However, rare patients, termed elite controllers, have a natural ability to control HIV infection in the absence of ART, but the mechanisms by which they achieve this phenotype have not been fully explored. This paper identifies one mechanism that may contribute to this natural resistance: some elite controllers have CD4+T cells that produce high levels of MIP chemokines, which block R5-tropic HIV entry. This mechanism could potentially be exploited to achieve a therapeutic effect in other HIV-seropositive individuals.

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HIV infection risk and condom use among sex workers in Senegal: evidence from the list experiment method

Health Policy and Planning ◽

10.1093/heapol/czz155 ◽

2020 ◽

Vol 35 (4) ◽

pp. 408-415

Author(s):

Aurélia Lépine ◽

Carole Treibich ◽

Cheikh Tidiane Ndour ◽

Khady Gueye ◽

Peter Vickerman

Keyword(s):

Treatment Group ◽

Hiv Infection ◽

Condom Use ◽

Sex Workers ◽

Infection Risk ◽

Hiv Positive ◽

Experiment Method ◽

List Experiment ◽

Hiv Negative

Abstract Social desirability bias, which is the tendency to under-report socially undesirable health behaviours, significantly distorts information on sensitive behaviours that is gained from self-reports. As a result, self-reported condom use among high-risk populations is thought to be systematically over-reported, and it is impossible to identify the determinants of condom use. The main objective of the article is to elicit unbiased information on condom use among female sex workers (FSWs) using the double list experiment method to analyse the role of HIV infection and exposure to HIV prevention methods in condom use. More specifically, the difference in levels of condom use between HIV-positive and HIV-negative FSWs is estimated. In addition, the role of FSWs’ registration and participation in a pre-exposure prophylaxis (PrEP) demonstration project in condom use is considered. A list experiment was designed to elicit condom use information from 786 FSWs in Senegal who were surveyed in 2015 and 2017. Using the list experiment method, participants were randomly assigned to one of two groups (treatment or control) and were asked to report the number of statements they agreed with. Respondents assigned to the control group were presented with three non-sensitive items, whereas those allocated to the treatment group were presented with the same three statements plus the sensitive item (e.g. ‘I used a condom during my last intercourse with a client’). Comparing the average number of sentences that were agreed with in both groups provides an estimation of the condom use rate in the treatment group and estimating such prevalence for several sub-groups allows the role of HIV infection risk in condom use to be identified. The percentage of FSWs using condoms in their last sexual intercourse with a client was 80% in 2015 and 78% in 2017, which was significantly lower than the 97% obtained in the face-to-face surveys in both waves. When estimating condom use among sub-groups with the list experiment method, we found that condom use among HIV-positive FSWs was only 34%, which was 47 percentage points lower than condom use among HIV-negative FSWs. We also found that registered FSWs are more likely to use condoms than clandestine FSWs. However, we did not find any difference in condom use between FSWs who were enrolled in the PrEP demonstration project and those who were not enrolled. Health policies should therefore aim to increase condom use among HIV-positive FSWs.

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