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Find video protocols related to scientific articles indexed in Pubmed.
Longitudinal Changes in Peripheral Blood NK Cells During the First Year of HIV-1 Infection in CD4Low and CD4High Patient Groups.
AIDS Res. Hum. Retroviruses
PUBLISHED: 11-12-2014
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Abstract Natural killer (NK) cells may modulate the pathogenesis of primary HIV-1 infection. However, the relationship between the number and function of NK cells during an acute HIV-1 infection and HIV-1 disease progression remains to be elucidated. In this study, we enrolled two distinct patient groups. One group progressed to where their CD4 cell counts fell below 200 cells/?l within 2 years (CD4Low group), while the CD4 cell counts of the other group remained above 500 cells/?l for over 2 years (CD4High group). We compared the number and function of NK cells during the first year of HIV-1 infection between the two distinct groups. We found that the number of total NK cells and the number of cells in the CD56(dim)CD16(pos) subset rapidly decreased in both groups during early HIV-1 infection. The absolute number of total NK cells and CD56(dim)CD16(pos) NK cells was significantly higher in the CD4High group when compared to the CD4Low group during the first month of infection. No significant difference between the numbers of CD56(bright)CD16(neg) NK cells of the two groups was observed. However, more CD56(neg)CD16(pos) NK cells were found in the CD4Low group than in the CD4High group. We also found that NK cell function increased within the first 3 months of HIV-1 infection in the CD4High group and then exhibited a decreasing trend. However, in the CD4Low group, NK cell function did not increase significantly within the first 3 months of HIV-1 infection but then gradually increased. We concluded, therefore, that robust NK functioning cells that are present during an acute HIV-1 infection might be beneficial in controlling HIV-1 disease progression.
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Acute HIV Infection Is Beneficial for Controlling Chronic Hepatitis B.
Clin. Infect. Dis.
PUBLISHED: 09-09-2014
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?Coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) is common. Most studies have concentrated on the effects of chronic HIV infection on HBV infection; however, studies on the effects of acute HIV infection on HBV infection are especially important to elucidate the potential mechanisms leading to complications from HIV/HBV coinfection.
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?? T cells are involved in acute HIV infection and associated with AIDS progression.
PLoS ONE
PUBLISHED: 09-04-2014
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Early diagnosis is vital to HIV control. ?? T cells play critical roles in viral infections, but their activation in acute HIV infected patients and follow up to 18 months has not been described.
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Longitudinal Changes in Total, 2-LTR Circular, and Integrated HIV-1 DNA During the First Year of HIV-1 Infection in CD4Low and CD4High Patient Groups with HIV-1 Subtype AE.
Viral Immunol.
PUBLISHED: 09-04-2014
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Abstract The level of viral DNA in early HIV-1 infection is an important parameter in the prediction of disease progression. Few data have been published on the dynamics of HIV-1 DNA during the first year of HIV infection. In this study, two distinct HIV-1 patient groups were enrolled. Group 1 (CD4High group) maintained their CD4 above 450 cells/?L within 1 year, while Group 2 (CD4Low group) progressed to CD4 below 300 cells/?L. The amounts of total, 2-long terminal repeat (2-LTR) circular, and integrated HIV-1 DNA were determined in the peripheral blood mononuclear cells at 1, 3, 6, and 12 months after HIV infection. Reductions in the amount of total and integrated HIV-1 DNA were detected in the CD4High group during the first year of HIV infection but not in the CD4Low group. Disease progression may be related to the body's ability to control HIV-1 DNA during early HIV-1 infection.
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Compare mDCs and pDCs between two distinct patients groups in acute HIV-1 infection.
AIDS Res Ther
PUBLISHED: 07-31-2014
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The role of DCs in primary HIV-1 infection remains uncertain. In this study, we enrolled two different groups of subjects with acute HIV-1 infection. One group progressed to CD4 counts below 200 cells/?l within 2 years of HIV-1 infection (CD4 Low Group), while the other group maintained CD4 counts above 500 cells/?l (CD4 High Group). We did not find statistical difference in the pDC number between the two groups during acute HIV-1 infection. However, the mDC number was significantly lower in the CD4 Low Group than in the CD4 High Group.
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Plasmacytoid dendritic cells mediate synergistic effects of HIV and lipopolysaccharide on CD27+ IgD- memory B cell apoptosis.
J. Virol.
PUBLISHED: 07-23-2014
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The effects of heightened microbial translocation on B cells during HIV infection are unknown. We examined the in vitro effects of HIV and lipopolysaccharide (LPS) on apoptosis of CD27+ IgD- memory B (mB) cells from healthy controls. In vivo analysis was conducted on a cohort of 82 HIV+ donors and 60 healthy controls. In vitro exposure of peripheral blood mononuclear cells (PBMCs) to LPS and HIV led to mB cell death via the Fas/Fas ligand (FasL) pathway. Plasmacytoid dendritic cells (pDCs) produced FasL in response to HIV via binding to CD4 and chemokine coreceptors. HIV and LPS increased Fas expression on mB cells in PBMCs, which was dependent on the presence of pDCs and monocytes. Furthermore, mB cells purified from PBMCs and pretreated with both HIV and LPS were more sensitive to apoptosis when cocultured with HIV-treated pDCs. Blocking the interferon receptor (IFNR) prevented HIV-stimulated FasL production in pDCs, HIV-plus-LPS-induced Fas expression, and apoptosis of mB cells. In vivo or ex vivo, HIV+ donors have higher levels of plasma LPS, Fas expression on mB cells, and mB cell apoptosis than controls. Correspondingly, in HIV+ donors, but not in controls, a positive correlation was found between plasma FasL and HIV RNA levels and between Fas expression on mB cells and plasma LPS levels. This work reveals a novel mechanism of mB cell apoptosis mediated by LPS and HIV through the Fas/FasL pathway, with key involvement of pDCs and type I IFN, suggesting a role for microbial translocation in HIV pathogenesis.
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Higher HIV DNA in CD4+ naïve T-cells during acute HIV-1 infection in rapid progressors.
Viral Immunol.
PUBLISHED: 06-03-2014
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AbFew reports have shown the relationship between the distribution of human immunodeficiency virus type 1 (HIV-1) proviral DNA in CD4 subsets during acute HIV-1 infection and HIV disease progression. In this study, we enrolled two groups with distinct differences in disease progression. The CD4 counts of one group fell below 200 cells/?L within 2 years (rapid progressors), whereas the other group maintained CD4 counts above 500 cells/?L (slow progressors). We collected blood samples during Fiebig stage III-IV of the two groups, and sorted CD4+ naïve, central memory, and effector memory lymphocytes. Real-time polymerase chain reaction was used to quantify HIV-1 DNA of the subsets. We found that HIV-1 DNA content was higher in memory T-cells than in naïve cells in both groups, and a higher HIV DNA content was found in naïve CD4+ T-cells during acute HIV-1 infection in rapid progressors. This suggests that higher HIV DNA in naïve CD4+ T-cells may associated with rapid progression.
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Combination of lithium chloride and pEGFP-N1-BmK CT effectively decreases proliferation and migration of C6 glioma cells.
Cytotechnology
PUBLISHED: 04-29-2014
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Deleterious invasiveness of glioma cells into the normal brain tissue is endorsed by its inherent ability to regulate the receptor-mediated adhesive properties, extracellular matrix degradation and remodeling and elevated secretory ability of metalloproteinase (MMPs) such as MMP-2. By doing so, it will create an intercellular space for the invasion of glioma cells. Here, we reported that combination of gene therapy Buthus martensii Karsch (BmK) CT, a type of scorpion toxin peptide, with lithium chloride (LiCl), clinically used as mood stabilizer, could inhibit the migration and invasion of C6 glioma cells. The results showed that concomitant administration of LiCl and pEGFP-N1-BmK CT on glioma cells would hamper pro-MMP2 secretion and in the meantime, inhibited its proliferation in a synergistic manner. These results try to extrapolate the potential interplay between the combined treatment of LiCl and BmK CT with signaling pathways ?-catenin, MMP, GSK-3 in C6 glioma cells. This strategy can stand for a novel approach designated for the development of a new method for glioma therapy.
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Regulatory B cells correlate with HIV disease progression.
Microbiol. Immunol.
PUBLISHED: 03-28-2014
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A rare subset of IL-10-producing B cells, named Breg, was recently identified in mice and humans. Currently, there are no unified cell surface markers to identify Breg, and the relationship between the frequency of Breg and HIV disease progression in chronic HIV infection is unclear. In the present study, we determined whether the cell surface markers of Breg reported for other diseases are suitable for identifying Breg in HIV-infected patients. In addition, we examined the relationship between Breg and HIV disease progression. We found that Breg frequency correlated positively with viral load and negatively with CD4 count in chronic HIV infection. Following antiretroviral treatment, the CD4 count increased and the frequency of Breg decreased stepwise. There was no difference in IL-10 expression of CD1d(hi) or CD1d(lo) cells isolated from HIV-infected patients. Therefore, CD1d may not be a marker of Breg in HIV-infected patients.
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Distortion of memory V?2 ?? T cells contributes to immune dysfunction in chronic HIV infection.
Cell. Mol. Immunol.
PUBLISHED: 03-09-2014
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?? T cells play important roles in innate immunity as the first-line of defense against infectious diseases. Human immunodeficiency virus (HIV) infection disrupts the balance between V?1 T cells and V?2 T cells and causes dysfunction among ?? T cells. However, the biological mechanisms and clinical consequences of this disruption require further investigation. In this study, we performed a comprehensive analysis of phenotype and function of memory ?? T cells in cohorts of Chinese individuals with HIV infection. We found a dynamic change in memory V?2 ?? T cells, skewed toward an activated and terminally differentiated effector memory phenotype TEMRA V?2 ?? T cell, which may account for the dysfunction of V?2 ?? T cells in HIV disease. In addition, we found that IL-17-producing ?? T cells were significantly increased in HIV-infected patients with fast disease progression and positively correlated with HLA-DR(+) ?? T cells and CD38(+)HLA-DR(+) ?? T cells. This suggests the IL-17 signaling pathway is involved in ?? T-cell activation and HIV pathogenesis. Our findings provide novel insights into the role of V?2 T cells during HIV pathogenesis and represent a sound basis on which to consider immune therapies with these cells.Cellular & Molecular Immunology advance online publication, 15 September 2014; doi:10.1038/cmi.2014.77.
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IL-6 and IFN? are elevated in severe mumps cases: a study of 960 mumps patients in China.
J Infect Dev Ctries
PUBLISHED: 02-13-2014
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Mumps is a common infectious disease. Epidemics of mumps are reported globally every year and represent a threat to public health, especially in China and other developing countries.
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Interleukin-8 is elevated in severe hand, foot, and mouth disease.
J Infect Dev Ctries
PUBLISHED: 01-16-2014
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Enterovirus 71 (EV71) infections can cause hand, foot, and mouth disease (HFMD), which is a potentially fatal illness in children. Epidemics of HFMD are seen every year globally and present an increasing threat to public health worldwide.
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Study on risk factors for severe hand, foot and mouth disease in China.
PLoS ONE
PUBLISHED: 01-01-2014
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Epidemics of HFMD are elevated every year globally, especially in mainland China. The disease now presents as an increasing threat to public health worldwide.
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Increasing Occurrence of Antimicrobial-Resistant Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae Isolates in China.
Clin. Infect. Dis.
PUBLISHED: 10-07-2013
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Background.?New hypervirulent variants of Klebsiella pneumoniae (hvKP) are emerging globally, most of which exhibit antimicrobial susceptibility. Methods.?A retrospective study was conducted in 88 patients with cultures positive for K. pneumoniae hospitalized in the Beijing Youan Hospital from April 2010 to June 2012. The clinical and molecular data of the hvKP isolates (defined as string test positive) were compared with those of the classic K. pneumoniae (cKP) isolates. Results.?Overall, 33.0% (29/88) of K. pneumoniae isolates were hvKP. Univariate analysis revealed the following risk factors for hvKP: virulence gene rmpA (odds ratio [OR], 16.92 [95% confidence interval {CI}, 4.842-59.145]), capsule antigens K1 (OR, 3.355 [95% CI, 1.153-9.768]) and K2 (OR, 9.280 [95% CI, 0.987-87.250]), alcoholic hepatitis (OR, 7.435 [95% CI, 1.397-39.572]), liver abscess (OR, 9.068 [95% CI, 1.747-47.061]), metastatic infection (OR, 2.752 [95% CI, 1.100-6.886]), community-acquired infection (OR, 10.432 [95% CI, 3.623-30.033]), sputum isolation (OR, 0.312 [95% CI, .095-1.021]), and HIV infection (<0.001 [not applicable]). Multivariate analysis implicated rmpA (OR, 17.398 [95% CI, 4.224-71.668]) and community-acquired infection (OR, 6.844 [95% CI, 1.905-24.585]) as independent risk factors. The proportion of hvKP isolates increased from April to December 2010, January to September 2011, and October 2011 to June 2012 (to 25.5%, 26.7%, and 54.5%, respectively). Resistance to 14 of 19 tested antimicrobials was found to be significantly greater in cKP compared to hvKP. Importantly, resistance to all the tested antimicrobials, except carbapenems and amikacin, was observed in a proportion of hvKP strains, 17% (5/29) of which expressed extended-spectrum ?-lactamase. Furthermore, antimicrobial resistance in hvKP strains increased over time. Conclusions.?HvKP strains are being isolated from patients in China with increasing frequency and constitute an increasing proportion of K. pneumoniae strains, indicating an increasing propensity for the acquisition of antimicrobial resistance.
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Double Negative (DN) [CD3?CD4?CD8?] T cells correlate with disease progression during HIV infection.
Immunol. Invest.
PUBLISHED: 06-27-2013
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Although double negative T (DNT) cells (CD3?CD4?CD8?) share some characteristics with T regulatory cells, the relationship between DNT cells and disease progression in HIV infection is unclear. In this study, we analyzed the relationship between DNT cells and disease progression during the first 2 years of HIV infection. We found that DNT cell numbers tended to decrease with disease progression. There was a positive correlation between DNT cells and CD4 counts. The DNT cell numbers were significantly lower in the high viral load group compared with the low viral load group. Therefore, we conclude that DNT cells correlated with disease progression in HIV infection. These data provide valuable information for further understanding of the role of DNT cells during HIV infection.
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Aberrant production of soluble inducible T-cell co-stimulator (sICOS) and soluble programmed cell death protein 1 (sPD-1) in patients with chronic hepatitis C.
Mol Med Rep
PUBLISHED: 01-16-2013
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Previous studies have indicated that immune dysregulation is an important cause of HCV?mediated damage to the liver. Co?stimulation signals, including programmed cell death protein 1 (PD?1) and inducible T?cell co?stimulator (ICOS), have been demonstrated to be involved in the pathogenesis of HCV. The purpose of this study was to investigate the soluble PD?1 (sPD?1) and soluble ICOS (sICOS) serum levels in chronic HCV patients, and to elucidate the association of sPD?1 and sICOS levels with pathological injury of chronic HCV infection. Sixty?three patients with chronic HCV and 30 normal controls were recruited for this study. The serum concentration levels of sPD?1 and sICOS were measured by enzyme?linked immunosorbent assay, and the mRNA levels of PD?1 and ICOS were detected using real?time RT?PCR. The serum sPD?1 and sICOS levels were significantly elevated in the chronic HCV patient group compared with the normal control group. Furthermore, the relative mRNA expression levels of these proteins were also increased in chronic HCV patients. sPD?1 and sICOS serum levels were significantly correlated with anti?HCV antibody levels, but not with HCV RNA. Aberrant sPD?1 and sICOS serum levels may reflect the dysregulation of T?cell activation, and are associated with the pathological injury of chronic HCV infection.
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Diagnostic performance of interferon-gamma releasing assay in HIV-infected patients in China.
PLoS ONE
PUBLISHED: 01-01-2013
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Active tuberculosis infection represents a very common and significant threat to HIV-infected patients. But measures to accurately detect it are limited.
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Central memory CD4 cells are an early indicator of immune reconstitution in HIV/AIDS patients with anti-retroviral treatment.
Immunol. Invest.
PUBLISHED: 05-12-2011
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The number of central memory cells among the CD4+ T cells and the of activation of CD8+ T cells is believed to be a better indicator of immune restoration in patients on antiretroviral therapy (ART) than the absolute numbers of CD4(+) and CD8+ T cells alone. In the current study, we investigated the changes in the CD4(+) T cell subsets and their association with immune reconstitution and immune activation at early stages of ART. A prospective study was performed in 21 asymptomatic treatment-naive HIV-infected patients with CD4(+) T cells less than 350 cells/?l. Blood samples were evaluated at base line, and at 2, 4, 8 and 12 weeks post antiretroviral therapy (ART). A biphasic increase of CD4(+) T cells, central memory CD4 cells (CD4 CM) and CD4 naïve cells were observed after ART, with a rapid increase before week 4. Change in CD4 CM at week 4 positively correlated with the change in CD4(+) T cells at weeks 12 post ART, and negatively correlated with the change in CD8(+)CD38(+) T cells at weeks 12 post ART. We conclude that CD4 CM cells are a major contributor to early immune reconstitution in treatment-naive HIV-infected patients with delayed ART, and might be an early indicator for immune reconstitution.
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Preferential depletion of CD2(low) plasmacytoid dendritic cells in HIV-infected subjects.
Cell. Mol. Immunol.
PUBLISHED: 04-25-2011
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Plasmacytoid dendritic cells (pDCs) are decreased in number and are functionally impaired in HIV act reasons for pDCs depletion are still unknown. It was recently reported that pDCs can be divided into two functionally distinct populations based on their CD2 expression level. To determine how the CD2(high) and CD2(low) populations are affected by HIV infection, we analyzed their frequencies in the peripheral blood of HIV-infected subjects and healthy controls. We found that the CD2(low) pDC subset was preferentially depleted in infected individuals. The frequency of CD2(low) pDCs correlated with the CD4(+) T-cell count but not with the plasma viral load. This finding furthers our understanding of the causes and consequences of pDC depletion during HIV infection.
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HIV-1 co-receptor usage based on V3 loop sequence analysis: preferential suppression of CXCR4 virus post HAART?
Immunol. Invest.
PUBLISHED: 04-25-2011
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Disease progression during human immunodeficiency virus type 1 (HIV-1) infection has been associated with a switch of viral coreceptor usage from CCR5 to CXCR4. The current study investigates the effect of anti retroviral therapy (ART) on the viral tropism in a group of patients based on the V3 loop sequence, in ART naïve patients prior to and 24 weeks after ART. Genomic DNA was extracted from the PBMCs of these patients, and the C2-V5 region of the HIV-1 env genes were cloned and sequenced. The coreceptor usage was predicated based on V3 loop amino acid sequences using Geno2pheno and PSSM programs. Our results indicate that following ART, the plasma viral loads of both CXCR4 and CCR5 viruses were significantly decreased. We observed a relatively higher ratio of R5 than X4 virus after 24 weeks of ART and both the positive charges and the net charges of the V3 regions were decreased significantly (p < 0.05) after ART. We conclude that ART significantly, reduced both X4 and R5 viruses with a preferential suppression of X4 virus. These data will help improve prognostic outcomes and help clinicians determine the course of treatment in patients who exhibit virologic failure while taking a CCR5 antagonist.
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Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy.
PLoS ONE
PUBLISHED: 04-16-2011
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Despite prolonged treatment with highly active antiretroviral therapy (HAART), the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment.
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Characteristics of CD8+ T cell subsets in Chinese patients with chronic HIV infection during initial ART.
AIDS Res Ther
PUBLISHED: 03-25-2011
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CD8+ T cells may play an important role in protecting against HIV. However, the changes of CD8+ T cell subsets during early period of ART have not been fully studied.
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A versatile vector for the production of pseudotyped viruses expressing gp120 antigens from different clades of primary HIV-1 isolates.
J. Virol. Methods
PUBLISHED: 08-13-2010
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A novel HIV-1 Env expression vector (SF162-Z) was developed by introducing two new cloning sites on the backbone of an existing vector that produces a full length Env from HIV-1 SF162 isolate. These sites facilitate the swapping of the gp120 portion of the SF162 Env with matching gp120 antigens from HIV-1 isolates of different genetic clades. Final production of functional pseudotyped viruses will express chimeric Env antigens, including gp41 of the parental SF162 and gp120 from other primary isolates. This system is useful for testing the neutralizing sensitivity of partial env gene products frequently identified in viral quasi species in patients infected with HIV or when only partial gp120 gene products are available.
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Increased turnover of FoxP3high regulatory T cells is associated with hyperactivation and disease progression of chronic HIV-1 infection.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 06-30-2010
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To characterize the homeostasis of CD4FoxP3 regulatory T cells (Treg) and its association with immune hyperactivation in the disease progression of chronic HIV-1 infection.
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The decrease of regulatory T cells correlates with excessive activation and apoptosis of CD8+ T cells in HIV-1-infected typical progressors, but not in long-term non-progressors.
Immunology
PUBLISHED: 08-01-2009
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Persistent HIV infection results in a decrease in absolute counts of CD4(+) CD25(+) regulatory T cells (Treg). To investigate the role of decreased Treg counts in the regulation of excessive activation and apoptosis of CD8(+) T cells in human immunodeficiency virus (HIV)-1 infection, we characterized Treg in 83 HIV-1-infected individuals, including 19 long-term non-progressors (LTNPs) and 51 typical progressors (TPs) who were treatment-naïve, and 13 AIDS patients on highly active antiretroviral therapy (HAART), of whom nine were complete responders (CRs) and the remaining four were non-responders (NRs) to the treatment. TPs but not LTNPs had a significant decrease in absolute counts of circulating Treg, which was inversely correlated with the activation and apoptosis of CD8(+) T cells. Efficient HAART was found to increase Treg counts in CR patients and temper the excessive activation and apoptosis of CD8(+) T cells. Moreover, isolated Treg significantly inhibited the spontaneous and anti-CD3-induced apoptosis of CD8(+) T cells in a dose-dependent manner in vitro. Thus, our findings indicate that the decrease in Treg closely correlates with the increase in apoptotic CD8(+) T cells and disease progression in chronic HIV-1 infection, and that Treg may play a key role in maintaining the balance between the amount and quality of CD8(+) T cells in HIV-1 infection. Manipulation of Treg function may be a promising strategy for immune therapy of this disease.
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pEGFP-N1-mediated BmK CT expression suppresses the migration of glioma.
Cytotechnology
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Gliomas can diffuse into the normal brain and this invasion of glioma cells involves modification of receptor-mediated adhesive properties of tumor cells, degradation and remodeling of extracellular matrix by tumor-secreted metalloproteinase (MMPs) such as MMP-2, consequently creating an intercellular space for invasion of glioma cells. BmK CT, one of the key toxins in scorpion Buthus martensii Karsch venom, is a novel blocker of the chloride ion channel and MMP-2. In this report, a recombinant plasmid pEGFP-N1-BmK CT was constructed and characterized by in vitro studies. The results showed that pEGFP-N1 mediated BmK CT expression displayed a high activity in suppressing cell migration via MMP-2. The potential therapeutic effect of pEGFP-N1 mediated BmK CT against rat glioma C6 cells was assessed and its potential mechanism was elucidated. It represented an approach for developing a novel therapeutic agent-recombinant plasmid pEGFP-N1-BmK CT as an efficient and powerful adjuvant.
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Serum neutralizing activities from a Beijing homosexual male cohort infected with different subtypes of HIV-1 in China.
PLoS ONE
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Protective antibodies play a critical role in an effective HIV vaccine; however, eliciting antibodies to block infection by viruses from diverse genetic subtypes remains a major challenge. As the worlds most populous country, China has been under the threat of at least three major subtypes of circulating HIV-1 viruses. Understanding the cross reactivity and specificities of serum antibody responses that mediate broad neutralization of the virus in HIV-1 infected Chinese patients will provide valuable information for the design of vaccines to prevent HIV-1 transmission in China. Sera from a cohort of homosexual men, who have been managed by a major HIV clinical center in Beijing, China, were analyzed for cross-sectional neutralizing activities against pseudotyped viruses expressing Env antigens of the major subtype viruses (AE, BC and B subtypes) circulating in China. Neutralizing activities in infected patients blood were most capable of neutralizing viruses in the homologous subtype; however, a subset of blood samples was able to achieve broad neutralizing activities across different subtypes. Such cross neutralizing activity took 1-2 years to develop and CD4 binding site antibodies were critical components in these blood samples. Our study confirmed the presence of broadly neutralizing sera in Chinas HIV-1 patient population. Understanding the specificity and breadth of these neutralizing activities can guide efforts for the development of HIV vaccines against major HIV-1 viruses in China.
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Plasma IP-10 is associated with rapid disease progression in early HIV-1 infection.
Viral Immunol.
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Cytokines play key roles in modulating disease progression in simian immunodeficiency virus/human immunodeficiency virus (SIV/HIV) infection. There are a few studies on the relationship between early cytokines and HIV disease prognosis. In this study, we first report the relationship based on two groups with clearly different disease progression. We found that IP-10 was the only cytokine among the 26 cytokines tested that was always positively correlated with disease progression, and was associated with the time for CD4 counts to fall below 200 cells/?L during Fiebig stages III-V in HIV-1 infection. This suggests that high IP-10 levels in the blood are associated with rapid disease progression during Fiebig stages III-V in HIV-1 infection.
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Primary CXCR4 co-receptor use in acute HIV infection leads to rapid disease progression in the AE subtype.
Viral Immunol.
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This is a comparative study of HIV co-receptor usage in the early stages of HIV infection between two distinct patient groups, one with a low CD4 count (group 1), and the other with a high CD4 count (group 2). Group 1 progressed to a CD4 count below 200 cells/?L within 2 y, while group 2 had a CD4 count above 500 cells/?L within 2 y. Viral RNA was extracted from the plasma of these patients, and the C2-V5 region of the HIV-1 env genes were cloned and sequenced. The co-receptor usage was predicated based on V3 loop amino acid sequences using Geno2pheno and PSSM programs. Our results indicate that in acute HIV infection of rapid progressors (low CD4 count; group 1), the primary co-receptor usage is CXCR4, while in the high CD4 count group (group 2), the co-receptor usage is predominantly CCR5. One-year follow-up data from these patients showed no obvious change in HIV co-receptor usage in either group. Sequence analysis of patients from both study groups showed prevalence of the AE subtype, and therefore we can speculate that the CXCR4 co-receptor may be the primary HIV-1 co-receptor used in the HIV-1 AE subtype, and may be responsible for rapid HIV-1 disease progression in the MSM cohort.
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Longitudinal changes of peripheral blood DC subsets and regulatory T cells in Chinese chronic HIV-1-infected patients during antiretroviral therapy.
PLoS ONE
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It has been emphasized that chronic generalized immune dysfunction is the leading event in the pathogenesis of HIV infection, in which the contribution of dendritic cells (DCs) and regulatory T cells (Tregs) should not be underestimated. In current study, we assessed the longitudinal changes of peripheral blood DC subsets and Tregs in chronically asymptomatic treatment-naive HIV-1-infected patients during 60 weeks of antiretroviral therapy (ART), and compared with those in healthy controls and long term non-progressors (LTNPs). Blood samples were collected at week 0, 4, 12, 24, 48 and 60 of treatment to measure the counts of DC subsets and Tregs by flow cytometry and IFN-a plasma levels by ELISA. The counts of myeloid dendritic cells (mDCs) increased during ART, reaching similar levels to healthy controls at week 60 post ART but still lower than those of LTNPs. In HIV-1-infected patients, the mDCs counts were directly correlated with CD4 counts during ART. Changes in mDCs at week 8 were positively correlated with the changes in CD4 counts at week 60 post ART. However, the counts and function of plasmacytoid dendritic cells (pDCs) remained relatively stable during ART, and similar to those in healthy controls and LTNPs. The percentage of Tregs increased before ART and normalized after ART. Importantly, we found pDCs counts were associated with percentage of Tregs during ART, which may help in understanding of the role of these cells in HIV infection.
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