scholarly journals A feline immunodeficiency virus vif-deletion mutant remains attenuated upon infection of newborn kittens

2007 ◽  
Vol 88 (10) ◽  
pp. 2793-2799 ◽  
Author(s):  
Xiaoying Shen ◽  
Christian M. Leutenegger ◽  
Kelly Stefano Cole ◽  
Niels C. Pedersen ◽  
Ellen E. Sparger
Keyword(s):  
T Cell ◽  
Feline Immunodeficiency Virus ◽  
Peripheral Blood ◽  
Deletion Mutant ◽  
Cell Subset ◽  
Cd4 T Cell ◽  
Wild Type ◽  
Immunodeficiency Virus ◽  
Antiviral Antibody ◽  
Cd4 T Cell Count

This report characterizes lentivirus attenuation associated with a vif mutation by inoculation of newborn kittens with a vif-deleted feline immunodeficiency virus provirus plasmid (FIV-pPPRΔvif). Virus in peripheral blood, antiviral antibody or CD4 T-cell count alterations were not detected in kittens inoculated with FIV-pPPRΔvif plasmid, with the exception of one kitten that demonstrated FIV Gag antibody production at 42 weeks after inoculation. In contrast, wild-type FIV-pPPR-infected kittens were viraemic, seropositive and exhibited a decrease in the CD4 T-cell subset in peripheral blood. Interestingly, FIV-specific T-cell proliferative responses detected at 32 and 36 weeks after infection were comparable for both FIV-pPPRΔvif- and wild-type FIV-pPPR-inoculated kittens and suggested the possibility of a discreet tissue reservoir supporting sustained FIV-pPPRΔvif expression or replication. Overall, these findings confirmed that the severe virus attenuation for both replication and pathogenicity exhibited by a vif-deleted FIV mutant is similar for both neonatal and adult hosts.

scholarly journals Simian Immunodeficiency Virus Promoter Exchange Results in a Highly Attenuated Strain That Protects against Uncloned Challenge Virus

2004 ◽  
Vol 78 (3) ◽  
pp. 1080-1092 ◽  
Author(s):  
Philippe Blancou ◽  
Nicole Chenciner ◽  
Raphaël Ho Tsong Fang ◽  
Valérie Monceaux ◽  
Marie-Christine Cumont ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Parental Virus ◽  
Wild Type ◽  
Activation Markers ◽  
Challenge Virus ◽  
Immunodeficiency Virus

ABSTRACT Among the many simian immunodeficiency virus (SIV) immunogens, only live attenuated viral vaccines have afforded strong protection to a natural pathogenic isolate. Since the promoter is crucial to the tempo of viral replication in general, it was reasoned that promoter exchange might confer a novel means of attenuating SIV. The core enhancer and promoter sequences of the SIV macaque 239nefstop strain (NF-κB/Sp1 region from −114 bp to mRNA start) have been exchanged for those of the human cytomegalovirus immediate-early promoter (CMV-IE; from −525 bp to mRNA start). During culture of the resulting virus, referred to as SIVmegalo, on CEMx174 or rhesus macaque peripheral blood mononuclear cells, deletions arose in distal regions of the CMV-IE sequences that stabilized after 1 or 2 months of culture. However, when the undeleted form of SIVmegalo was inoculated into rhesus macaques, animals showed highly controlled viremia during primary and persistent infection. Compared to parental virus infection in macaques, primary viremia was reduced by >1,000-fold to undetectable levels, with little sign of an increase of cycling cells in lymph nodes, CD4+ depletion, or altered T-cell activation markers in peripheral blood. Moreover, in contrast to wild-type infection in most infected animals, the nef stop mutation did not revert to the wild-type codon, indicating yet again that replication was dramatically curtailed. Despite such drastic attenuation, antibody titers and enzyme-linked immunospot reactivity to SIV peptides, although slower to appear, were comparable to those seen in a parental virus infection. When animals were challenged intravenously at 4 or 6 months with the uncloned pathogenic SIVmac251 strain, viremia was curtailed by ∼1,000-fold at peak height without any sign of hyperactivation in CD4+- or CD8+-T-cell compartment or increase in lymph node cell cycling. To date, there has been a general inverse correlation between attenuation and protection; however, these findings show that promoter exchange constitutes a novel means to highly attenuate SIV while retaining the capacity to protect against challenge virus.

scholarly journals Anti-cytomegalovirus Immunoglobulin G Is Linked to CD4 T-cell Count Decay in Human Immunodeficiency Virus (HIV) Elite Controllers

2020 ◽  
Author(s):  
Stephane Isnard ◽  
Rayoun Ramendra ◽  
John Lin ◽  
Sanket Kant ◽  
Brandon Fombuena ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Cell Count ◽  
Immunoglobulin G ◽  
Human Leukocyte ◽  
Cd4 T Cell ◽  
Elite Controllers ◽  
Leukocyte Antigen ◽  
Immunodeficiency Virus ◽  
Cd4 T Cell Count

Abstract Elite controllers (ECs) are people living with human immunodeficiency virus (HIV) who spontaneously control viral replication without antiretroviral therapy. We observed that elevated anti-cytomegalovirus (CMV) immunoglobulin G (IgG) levels correlated with annual CD4 T-cell count decay in ECs independently of age, sex, and human leukocyte antigen (HLA) type. Elevated anti-CMV titers may favor disease progression in ECs.

scholarly journals Gradually increased dyslipidemia  in human immunodeficiency virus infected male patients with tenofovir plus lamivudine plus efavirenz primary treatment: a 3-year follow-up study

2020 ◽  
Author(s):  
dafeng liu ◽  
Bennan Zhao ◽  
Xinyi Zhang ◽  
Fengjiao Gao ◽  
Jun Kang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Cd4 T Cell ◽  
Infected Male ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
Male Patients ◽  
Cd4 T Cell Count

Abstract IntroductionSince the start of highly active antiretroviral therapy (HAART) with TDF plus 3TC plus EFV, the long-term dynamic characteristics of lipid and purine metabolism in patients infected with human immunodeficiency virus (HIV) was unclear and worth studying.MethodsA prospective follow-up cohort study was the way. Sixty-one treatment-naive HIV infected male patients were divided into three groups based on the baseline CD4 + T cell count (26, 12, 23cases in < 200, from 200 to 350, > 350 three groups, respectively). Lipid and purine metabolism parameters of those patients within 144 weeks were analyzed.ResultTG, TC, LDL-c and HDL-c level all gradually increased within 144 weeks, but statistical significances of TC level and HDL-c level were only found (F = 4.214, 5.518, P = 0.001, 0.000 ,respectively). Moreover the percentage of hypercholesterolemia, hyper LDL cholesterolemia and hypertriglyceridemia all gradually increased, low HDL cholesterolemia gradually decreased, but there was only obvious difference of the latter (χ2 = 16.105, P = 0.0007).Furthermore the lower the baseline CD4 + T lymphocyte counts, the higher TG level, the lower TC level, LDL-c level and HDL-c level, but only significant difference of LDL-c level between three groups at baseline was found (F = 3.256,P = 0.0457).Although UA level and the percentages of hyperuricemia gradually increased within 144 weeks, but there was no significant difference between different follow-up time points groups and between three CD4 + T cell count groups (all P༞0.05).ConclusionsThese findings provide a reference for clinicians to monitor lipid metabolism parameters closely during long-term HAART with TDF plus 3TC plus EFV regimen.

scholarly journals Continued Elevation of Interleukin-18 and Interferon-γ After Initiation of Antiretroviral Therapy and Clinical Failure in a Diverse Multicountry Human Immunodeficiency Virus Cohort

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Ashwin Balagopal ◽  
Nikhil Gupte ◽  
Rupak Shivakoti ◽  
Andrea L. Cox ◽  
Wei-Teng Yang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Interferon Γ ◽  
Cd4 T Cell ◽  
Clinical Failure ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Cd4 T Cell Count

Abstract Background.  We assessed immune activation after antiretroviral therapy (ART) initiation to understand clinical failure in diverse settings. Methods.  We performed a case-control study in ACTG Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS). Cases were defined as incident World Health Organization Stage 3 or 4 human immunodeficiency virus (HIV) disease or death, analyzed from ART weeks 24 (ART24) to 96. Controls were randomly selected. Interleukin (IL)-6, interferon (IFN)-γ-inducible protein-10, IL-18, tumor necrosis factor-α, IFN-γ, and soluble CD14 (sCD14) were measured pre-ART and at ART24 in plasma. Continued elevation was defined by thresholds set by highest pre-ART quartiles (&gt;Q3). Incident risk ratios (IRRs) for clinical progression were estimated by Poisson regression, adjusting for age, sex, treatment, country, time-updated CD4+ T-cell count, HIV ribonucleic acid (RNA), and prevalent tuberculosis. Results.  Among 99 cases and 234 controls, median baseline CD4+ T-cell count was 181 cells/µL, and HIV RNA was 5.05 log10 cp/mL. Clinical failure was independently associated with continued elevations of IL-18 (IRR, 3.03; 95% confidence interval [CI], 1.27–7.20), sCD14 (IRR, 2.17; 95% CI, 1.02–4.62), and IFN-γ (IRR, 0.08; 95% CI, 0.01–0.61). Among 276 of 333 (83%) who were virologically suppressed at ART24, IFN-γ was associated with protection from failure, but the association with sCD14 was attenuated. Conclusions.  Continued IL-18 and sCD14 elevations were associated with clinical ART failure. Interferon-γ levels may reflect preserved immune function.

scholarly journals Downmodulation of CD3ε expression in CD8α + β − T cells of feline immunodeficiency virus-infected cats

2004 ◽  
Vol 85 (9) ◽  
pp. 2585-2589 ◽  
Author(s):  
Yorihiro Nishimura ◽  
Masayuki Shimojima ◽  
Eiji Sato ◽  
Yoshihiro Izumiya ◽  
Yukinobu Tohya ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Feline Immunodeficiency Virus ◽  
Peripheral Blood ◽  
Immune Status ◽  
Immunodeficiency Virus ◽  
Lower Expression

Feline immunodeficiency virus (FIV) infection in cats is associated with an increase of feline CD (fCD)8α + β − and fCD8α + β low cells in peripheral blood. To investigate these cells in more detail, an anti-fCD3ε mAb, termed NZM1, was generated, which recognizes the extracellular epitope of the fCD3ε molecule. The anti-fCD3ε mAb proved to be more suitable for identifying feline T cells than the anti-fCD5 one, which has been used as a pan-T-cell reagent in cats, because of the presence of fCD5+fCD3ε − cells among lymphocytes. Although the fCD8α + β − and fCD8α + β low cells in the FIV-infected cats expressed fCD3ε, a subset of fCD8α + β − cells expressed fCD3ε antigen at a lower level than the T cells whose phenotype was fCD4+, or fCD8α + β low. The lower expression of fCD3ε may be associated with the immune status of fCD8α + β − T cells.

scholarly journals Therapeutic Prediction of HIV-1 DNA Decay: A Multicenter Longitudinal Cohort Study

2020 ◽  
Author(s):  
Yongsong Yue ◽  
Yijia Li ◽  
Yizhi Cui ◽  
Nidan Wang ◽  
Yunda Huang ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Count ◽  
Predictive Model ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cd4 T Cell ◽  
Peripheral Blood Mononuclear ◽  
Treatment Naïve ◽  
Hiv 1 ◽  
Cd4 T Cell Count

Abstract Background: Factors predicting peripheral blood total HIV-1 DNA size in chronically infected patients with successfully suppressed viremia remain unclear. Prognostic power of such factors are of clinical significance for making clinical decisions.Methods: Total HIV-1 DNA in blood at baseline, 12, 24, 48, 96, and 288 weeks after combined antiretroviral therapy (cART) initiation in 607 treatment-naïve patients with chronic HIV-1 infection were quantified. Generalized estimating equations and logistic regression methods were used to derive and validate a predictive model of total HIV-1 DNA after 96 weeks of cART.Results: The total HIV-1 DNA rapidly decreased from baseline [mean = 3.04 log10 copies/106 peripheral blood mononuclear cells (PBMCs)] to week 24 (mean = 2.51 log10 copies/106 PBMCs), and leveled off afterwards. Of the 490 patients who had successful HIV-1 RNA suppression by 96 w post-cART, 92 (18.8%) had a low total HIV-1 DNA count (<100 copies/106 PBMCs) at week 96. In the predictive model, lower baseline total HIV-1 DNA [risk ratio (RR) = 0.08, per 1 log10 copies/106 PBMCs, P < 0.001] and higher baseline CD4+ T cell count (RR = 1.72, per 100 cells/μL, P < 0.001) were significantly associated with a low total HIV-1 DNA count at week 96. In an independent cohort of 117 patients, this model achieved a sensitivity of 75.00% and specificity of 69.52%.Conclusions: The derived model based on baseline total HIV-1 DNA and CD4+ T cell count provides a useful prognostic tool in predicting HIV-1 DNA reservoir control during cART.

scholarly journals Physician Decisions to Defer Antiretroviral Therapy in Key Populations: Implications for Reducing Human Immunodeficiency Virus Incidence and Mortality in Malaysia

2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Enrico G. Ferro ◽  
Gabriel J. Culbert ◽  
Jeffrey A. Wickersham ◽  
Ruthanne Marcus ◽  
Alana D. Steffen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
People Who Inject Drugs ◽  
Cd4 T Cell ◽  
Key Populations ◽  
Incidence And Mortality ◽  
Immunodeficiency Virus ◽  
Cd4 T Cell Count

Abstract Background Antiretroviral therapy (ART) is recommended for all people living with human immunodeficiency virus (HIV), yet physician attitudes and prescribing behaviors toward members of key risk populations may limit ART access and undermine treatment as prevention strategies. Methods Physicians in Malaysia (N = 214) who prescribe antiretroviral therapy (ART) responded in an Internet-based survey to hypothetical clinical scenarios of HIV patients, varying by key risk population and CD4+ T-cell count, on whether they would initiate or defer ART compared with a control patient with sexually acquired HIV. Results The proportion of physicians who would defer ART in patients with advanced HIV (CD4 = 17 cells/μL) was significantly higher (P &lt; .0001) for 4 key populations, including people who inject drugs ([PWID] 45.3%) or consume alcohol (42.1%), released prisoners (35.0%), and those lacking social support (26.6%), compared with a control patient (4.2%). People who inject drugs with advanced HIV (CD4 = 17 cells/μL) were 19-fold (adjusted odds ratio [AOR] = 18.9; 95% confidence interval [CI], 9.8–36.5) more likely to have ART deferred compared with the control. This effect was partially mitigated for PWID receiving methadone (AOR = 2.9; 95% CI, 1.5–5.7). At the highest CD4+ T-cell count (CD4 = 470 cells/μL), sex workers (AOR = 0.55; 95% CI, .44–.70) and patients with an HIV-uninfected sexual partner (AOR = 0.43; 95% CI, .34–.57) were significantly less likely to have ART deferred. Conclusions Physicians who prescribe antiretroviral therapy in Malaysia may defer ART in some key populations including PWID and released prisoners, regardless of CD4+ T-cell count, which may help to explain very low rates of ART coverage among PWID in Malaysia. Reducing HIV incidence and mortality in Malaysia, where HIV is concentrated in PWID and other key populations, requires clinician-level interventions and monitoring physician adherence to international evidence-based treatment guidelines.

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