scholarly journals Integrin α4β7 Is Downregulated on the Surfaces of Simian Immunodeficiency Virus SIVmac239-Infected Cells

2010 ◽  
Vol 84 (13) ◽  
pp. 6344-6351 ◽  
Author(s):  
Melisa L. Budde ◽  
Jennifer J. Lhost ◽  
Dawn M. Dudley ◽  
Eva G. Rakasz ◽  
David H. O'Connor
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Immune Evasion ◽  
Lymphoid Tissue ◽  
De Novo ◽  
Ex Vivo ◽  
Viral Proteins ◽  
Flow Cytometry Assay ◽  
Immunodeficiency Virus ◽  
Infected Cells

ABSTRACT Simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infection results in an early and enduring depletion of intestinal CD4+ T cells. SIV and HIV bind integrin α4β7, thereby facilitating infection of lymphocytes that home to the gut-associated lymphoid tissue (GALT). Using an ex vivo flow cytometry assay, we found that SIVmac239-infected cells expressed significantly lower levels of integrin α4β7 than did uninfected cells. This finding suggested a potential viral effect on integrin α4β7 expression. Using an in vitro model, we confirmed that integrin α4β7 was downregulated on the surfaces of SIVmac239-infected cells. Further, modulation of integrin α4β7 was dependent on de novo synthesis of viral proteins, but neither cell death, the release of a soluble factor, nor a change in activation state was involved. Downregulation of integrin α4β7 may have an unappreciated role in the CD4 depletion of the mucosal-associated lymphoid compartments, susceptibility to superinfection, and/or immune evasion.

scholarly journals Nef Enhances Human Immunodeficiency Virus Replication and Responsiveness to Interleukin-2 in Human Lymphoid Tissue Ex Vivo

1999 ◽  
Vol 73 (5) ◽  
pp. 3968-3974 ◽  
Author(s):  
Svetlana Glushakova ◽  
Jean-Charles Grivel ◽  
Kalachar Suryanarayana ◽  
Pascal Meylan ◽  
Jeffrey D. Lifson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Lymphoid Tissue ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Dependent Manner ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Human Lymphoid Tissue ◽  
Hiv 1

ABSTRACT The nef gene is important for the pathogenicity associated with simian immunodeficiency virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (HIV-1) infection in humans. The mechanisms by which nef contributes to pathogenesis in vivo remain unclear. We investigated the contribution of nef to HIV-1 replication in human lymphoid tissue ex vivo by studying infection with parental HIV-1 strain NL4-3 and with anef mutant (ΔnefNL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than ΔnefNL4-3 did. Increased virus production with NL4-3 infection was associated with increased numbers of productively infected cells and greater loss of CD4+ T cells over time. While the numbers of productively infected T cells were increased in the presence of nef, the levels of viral expression and production per infected T cell were similar whether the nefgene was present or not. Exogenous interleukin-2 (IL-2) increased HIV-1 production in NL4-3-infected tissue in a dose-dependent manner. In contrast, ΔnefNL4-3 production was enhanced only marginally by IL-2. Thus, Nef can facilitate HIV-1 replication in human lymphoid tissue ex vivo by increasing the numbers of productively infected cells and by increasing the responsiveness to IL-2 stimulation.

scholarly journals Porcine reproductive and respiratory syndrome virus-infected alveolar macrophages contain no detectable levels of viral proteins in their plasma membrane and are protected against antibody-dependent, complement-mediated cell lysis

2006 ◽  
Vol 87 (8) ◽  
pp. 2341-2351 ◽  
Author(s):  
Sarah Costers ◽  
Peter L. Delputte ◽  
Hans J. Nauwynck
Keyword(s):  
Plasma Membrane ◽  
Immune Evasion ◽  
Alveolar Macrophages ◽  
Viral Proteins ◽  
Cell Lysis ◽  
Respiratory Syndrome Virus ◽  
Specific Antibodies ◽  
Infected Cells

Porcine reproductive and respiratory syndrome virus (PRRSV) can evade the host immune system, which results in prolonged virus replication for several weeks to several months. To date, the mechanisms of PRRSV immune evasion have not been investigated in detail. One possible immune-evasion strategy is to avoid incorporation of viral proteins into the plasma membrane of infected cells, as this prevents recognition by virus-specific antibodies and consequent cell lysis either by the classical complement pathway or by antibody-dependent, cell-mediated cytotoxicity. In this study, viral proteins were not observed in the plasma membrane of in vitro-infected macrophages by using confocal microscopy or flow cytometry. Subsequently, the sensitivity of PRRSV-infected macrophages towards antibody-dependent, complement-mediated cell lysis (ADCML) was determined by using an ADCML assay. A non-significant percentage of PRRSV-infected cells were killed in the assay, showing that in vitro PRRSV-infected macrophages are protected against ADCML. PRRSV proteins were not detected in the plasma membrane of in vivo-infected alveolar macrophages and ADCML was also not observed. Together, these data indicate that viral proteins are not incorporated into the plasma membrane of PRRSV-infected macrophages, which makes infected cells invisible to PRRSV-specific antibodies. This absence of viral proteins on the cell surface could explain the protection against ADCML observed for in vitro and in vivo PRRSV-infected macrophages, and may play a role in virus persistence.

scholarly journals Simian Immunodeficiency Virus-Specific CD8+ T Cells Recognize Vpr- and Rev-Derived Epitopes Early after Infection

2010 ◽  
Vol 84 (20) ◽  
pp. 10907-10912 ◽  
Author(s):  
Jonah B. Sacha ◽  
Matthew B. Buechler ◽  
Laura P. Newman ◽  
Jason Reed ◽  
Lyle T. Wallace ◽  
...  
Keyword(s):  
T Cells ◽  
Simian Immunodeficiency Virus ◽  
De Novo ◽  
Cell Epitope ◽  
Cytolytic Activity ◽  
Peptide Epitopes ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Infected Cells ◽  
Kinetics Of

ABSTRACT The kinetics of CD8+ T cell epitope presentation contribute to the antiviral efficacy of these cells yet remain poorly defined. Here, we demonstrate presentation of virion-derived Vpr peptide epitopes early after viral penetration and prior to presentation of Vif-derived epitopes, which required de novo Vif synthesis. Two Rev epitopes exhibited differential presentation kinetics, with one Rev epitope presented within 1 h of infection. We also demonstrate that cytolytic activity mirrors the recognition kinetics of infected cells. These studies show for the first time that Vpr- and Rev-specific CD8+ T cells recognize and kill simian immunodeficiency virus (SIV)-infected CD4+ T cells early after SIV infection.

scholarly journals Early Establishment and Antigen Dependence of Simian Immunodeficiency Virus-Specific CD8+ T-Cell Defects

2007 ◽  
Vol 81 (20) ◽  
pp. 10861-10868 ◽  
Author(s):  
Yvonne M. Mueller ◽  
Constantinos Petrovas ◽  
Duc H. Do ◽  
Susan R. Altork ◽  
Tracy Fischer-Smith ◽  
...  
Keyword(s):  
T Cells ◽  
Simian Immunodeficiency Virus ◽  
Ex Vivo ◽  
Rhesus Macaques ◽  
Viral Escape ◽  
In Vitro Assays ◽  
Effector Memory ◽  
Immunodeficiency Virus ◽  
Induced Apoptosis

ABSTRACT Differentiation and survival defects of human immunodeficiency virus (HIV)-specific CD8+ T cells may contribute to the failure of HIV-specific CD8+ T cells to control HIV replication. It is not known, however, whether simian immunodeficiency virus (SIV)-infected rhesus macaques show comparable defects in these virus-specific CD8+ T cells or when such defects are established during infection. Peripheral blood cells from acutely and chronically infected rhesus macaques were stained ex vivo for memory subpopulations and examined by in vitro assays for apoptosis sensitivity. We show here that SIV-specific CD8+ T cells from chronically SIV infected rhesus macaques show defects comparable to those observed in HIV infection, namely, a skewed CD45RA− CD62L− effector memory phenotype, reduced Bcl-2 levels, and increased levels of spontaneous and CD95-induced apoptosis of SIV-specific CD8+ T cells. Longitudinal studies showed that the survival defects and phenotype are established early in the first few weeks of SIV infection. Most importantly, they appear to be antigen driven, since most probably the loss of epitope recognition due to viral escape results in the reversal of the phenotype and reduced apoptosis sensitivity, something we observed also for animals treated with antiretroviral therapy. These findings further support the use of SIV-infected rhesus macaques to investigate the phenotypic changes and apoptotic defects of HIV-specific CD8+ T cells and indicate that such defects of HIV-specific CD8+ T cells are the result of chronic antigen stimulation.

scholarly journals Antiretroviral activity of the aminothiol WR1065 against Human Immunodeficiency virus (HIV-1) in vitro and Simian Immunodeficiency virus (SIV) ex vivo

2009 ◽  
Vol 6 (1) ◽  
pp. 24 ◽  
Author(s):  
Miriam C Poirier ◽  
Ofelia A Olivero ◽  
Andrew W Hardy ◽  
Genoveffa Franchini ◽  
Jennifer P Borojerdi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Simian Immunodeficiency Virus ◽  
Ex Vivo ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Antiretroviral Activity

scholarly journals Simian Immunodeficiency Virus Variants That Differ in Pathogenicity Differ in Fitness under Rapid Cell Turnover Conditions

2005 ◽  
Vol 79 (24) ◽  
pp. 15091-15098 ◽  
Author(s):  
Yegor Voronin ◽  
Julie Overbaugh ◽  
Michael Emerman
Keyword(s):  
Life Span ◽  
Simian Immunodeficiency Virus ◽  
Negative Influence ◽  
Relative Fitness ◽  
Set Point ◽  
Rapid Turnover ◽  
Immunodeficiency Virus ◽  
Infected Cells

ABSTRACT Simian immunodeficiency virus (SIV) has been shown to progress through a number of changes that lead to the emergence of pathogenic viral variants in macaques initially infected with a mildly cytopathic variant, SIVMneCL8. One of these late-stage isolates, SIVMne170, replicates to high levels in vivo and causes a rapid disease course when reintroduced into naïve macaques, resulting in a viral set point up to 3,000-fold higher than the set point of the parental virus, SIVMneCL8. However, in cell culture both viruses replicate with similar kinetics. One major difference between in vivo and in vitro cultures is the life span of the infected cells. Here, we manipulated the life span of infected cells in vitro, and we show that the fitness of SIVMne170 in cultures with a limited cell life span dramatically increased compared to its fitness in cultures with a nonlimited life span of cells. The increase in fitness was at least partially due to the fact that the rapid turnover system eliminates the negative influence of the cytopathic effects associated with replication of SIVMne170. Because the relative fitness of SIVMneCL8 and SIVMne170 observed in the rapid turnover system more accurately reflects their fitness in vivo, the system represents an improved approach to comparing relative fitness of viruses.

scholarly journals Native oligodeoxynucleotides specifically active against human immunodeficiency virus type 1 in vitro: a G-quartet-driven effect?

1996 ◽  
Vol 40 (9) ◽  
pp. 2034-2038 ◽  
Author(s):  
L Tondelli ◽  
F P Colonna ◽  
A Garbesi ◽  
S Zanella ◽  
M E Marongiu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
De Novo ◽  
Active Structure ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

Among a series of unmodified phosphodiester (PO)-oligodeoxynucleotides (PO-ODNs) complementary to some of the human immunodeficiency virus type 1 (HIV-1) regulatory genes, several PO-ODN sequences complementary to the vpr gene (PO-ODNs-a-vpr, where a-vpr is the antisense vpr sequence) emerged as potent inhibitors (at concentrations of 0.8 to 3.3 microM) of HIV-1 multiplication in de novo infected MT-4 cells, while they showed no cytotoxicity for uninfected cells at concentrations up to 100 microM. Unlike phosphorothioate counterparts, PO-ODN-a-vpr sequences were not inhibitory to HIV-2 multiplication in de novo infected C8166 cells and neither prevented the fusion between chronically infected and bystander CD4+ cells nor inhibited the activity of the HIV-1 reverse transcriptase in enzyme assays. Moreover, they were not inhibitory to HIV-1 multiplication in chronically infected cells. Delayed addition experiments showed that PO-ODNs-a-vpr inhibit an event in the HIV-1 replication cycle following adsorption to the host cell, but preceding reverse transcription. Structure-activity relationship studies indicated that the antiviral activity of the test PO-ODN-a-vpr sequences is not related to an antisense mechanism but to the presence, within the active sequences, of contiguous guanine residues. Physical characterization of the test PO-ODNs suggested that the active structure is a tetramer stabilized by G quartets (i.e., four G residues connected by eight hydrogen bonds).

scholarly journals AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Failure To Protect and Possible Enhancement of Challenge Infection by Four Cell-Based Vaccines Prepared with Autologous Lymphoblasts

2002 ◽  
Vol 76 (14) ◽  
pp. 6882-6892 ◽  
Author(s):  
Simone Giannecchini ◽  
Patrizia Isola ◽  
Olimpia Sichi ◽  
Donatella Matteucci ◽  
Mauro Pistello ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Low Dose ◽  
Ex Vivo ◽  
Virus Dose ◽  
Immunodeficiency Virus ◽  
Virus Model ◽  
Infected Cells ◽  
Failure To Protect ◽  
Model Failure

ABSTRACT Immunogenicity and protective activity of four cell-based feline immunodeficiency virus (FIV) vaccines prepared with autologous lymphoblasts were investigated. One vaccine was composed of FIV-infected cells that were paraformaldehyde fixed at the peak of viral expression. The other vaccines were attempts to maximize the expression of protective epitopes that might become exposed as a result of virion binding to cells and essentially consisted of cells mildly fixed after saturation of their surface with adsorbed, internally inactivated FIV particles. The levels of FIV-specific lymphoproliferation exhibited by the vaccinees were comparable to the ones previously observed in vaccine-protected cats, but antibodies were largely directed to cell-derived constituents rather than to truly viral epitopes and had very poor FIV-neutralizing activity. Moreover, under one condition of testing, some vaccine sera enhanced FIV replication in vitro. As a further limit, the vaccines proved inefficient at priming animals for anamnestic immune responses. Two months after completion of primary immunization, the animals were challenged with a low dose of homologous ex vivo FIV. Collectively, 8 of 20 vaccinees developed infection versus one of nine animals mock immunized with fixed uninfected autologous lymphoblasts. After a boosting and rechallenge with a higher virus dose, all remaining animals became infected, thus confirming their lack of protection.

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