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At least 1,531 records · Page 85Linked to original sources
PubMed1967

The detection of a viral interfering substance in the Shope papilloma and the Vx7 and Vx2 carcinomas.

In vivo assay of Shope papilloma protein extract and in vitro assay of extracts from Shope papilloma, Vx7 and Vx2 carcinomas showed strong interferon-like activity in the papilloma and moderate activity in the carcinomas. The interpretation is that the presence of viral nucleic acid in all three tumors stimulated the production of this substance even though fluorescent antibody studies reveal the protein coat only in the papilloma and Vx7.

Animals↗
PubMed1988

The endogenous mink cell focus-forming (MCF) gp70 linked to the Rmcf gene restricts MCF virus replication in vivo and provides partial resistance to erythroleukemia induced by Friend murine leukemia virus.

The Rmcf locus restricts the in vitro replication of mink cell focus-forming (MCF) viruses in cell cultures derived from mice carrying the resistance allele. Previously we reported that in cell cultures from first backcross progeny, this Rmcf-linked restriction segregates with the expression of an endogenous retroviral gp70 serologically related to that of MCF viruses. The current report details the results of genetic studies designed to examine the possible association of this endogenous gp70 with resistance of mice to Friend murine leukemia virus (F-MuLV)-induced erythroleukemia. This env gene segregates as a single dominant trait in (DBA/2 X IRW) X IRW progeny, in which the expression of the gene can be detected by serological techniques. Results indicated that the gp70- progeny developed leukemia at the same rate as the susceptible IRW parent, whereas the tempo of disease among the gp70+ progeny was significantly slower. However, the resistance mediated by this gene was only partial, since most of the gp70+ offspring eventually developed erythroleukemia when followed for 6 mo. This endogenous gp70 also segregated with a restriction to the expression of recombinant MCF viruses after infection with F-MuLV. Since in this study all unlinked genes segregated independently, this is direct evidence that MCF viruses participate in the induction of erythroleukemia.

Animals↗
PubMed1997

A study of the interferon antiviral mechanism: apoptosis activation by the 2-5A system.

The 2-5A system contributes to the antiviral effect of interferons through the synthesis of 2-5A and its activation of the ribonuclease, RNase L. RNase L degrades viral and cellular RNA after activation by unique, 2'-5' phosphodiester-linked, oligoadenylates [2-5A, (pp)p5' A2'(P5'A2')]n, n >=2. Because both the 2-5A system and apoptosis can serve as viral defense mechanisms and RNA degradation occurs during both processes, we investigated the potential role of RNase L in apoptosis. Overexpression of human RNase L by an inducible promoter in NIH3T3 fibroblasts decreased cell viability and triggered apoptosis. Activation of endogenous RNase L, specifically with 2-5A or with dsRNA, induced apoptosis. Inhibition of RNase L with a dominant negative mutant suppressed poly (I).poly (C)-induced apoptosis in interferon-primed fibroblasts. Moreover, inhibition of RNase L suppressed apoptosis induced by poliovirus. Thus, increased RNase L levels induced apoptosis and inhibition of RNase L activity blocked viral-induced apoptosis. Apoptosis may be one of the antiviral mechanisms regulated by the 2-5A system.

3T3 Cells↗
PubMed2002

The pathogenesis of hepatitis C virus is influenced by cytomegalovirus.

We investigated the effect of beta-herpesviruses on allograft failure and mortality, hepatitis C virus (HCV) replication, and liver histologic characteristics among 92 HCV-infected liver transplant recipients. Reactivation of cytomegalovirus (CMV) but not of human herpesvirus 6 (HHV-6) was independently associated with allograft failure and mortality (risk ratio, 3.71; 95% confidence interval, 1.64-8.39); allograft failure and mortality was observed in 48% of patients with CMV disease, 35% of patients with subclinical CMV infection, and 17% of patients without CMV infection (P=.0275). CMV reactivation was highly predictive of mortality (P<.001), regardless of whether it remained subclinical or evolved into CMV disease. Patients with CMV disease had a higher fibrosis stage (P=.05) and had a trend toward a higher hepatitis activity index (P=.10) and HCV load (P=.10) at 16 weeks after liver transplantation. The pathogenesis of HCV is influenced by its interaction with CMV but not with HHV-6.

Adult↗
PubMed2005

South African GB virus C isolates: interactions between genotypes 1 and 5 isolates and HIV.

GB virus C (GBV-C) is a common, apparently nonpathogenic human flavivirus that has been associated in some studies with prolonged survival in human immunodeficiency virus (HIV)-positive persons. There are 5 distinct GBV-C genotypes localized to specific geographic regions, and genotype 2 has been previously shown to inhibit HIV replication in vitro in lymphocyte cultures. We identified GBV-C virus isolates representing genotypes 1, 2, and 5 in samples from South African blood donors. GBV-C genotype 1 and 5 isolates replicated in lymphocyte culture, inhibited X4 and R5 HIV-1 isolates, and induced RANTES and stromal-derived factor-1 chemokines in vitro. Thus, African GBV-C genotypes can inhibit HIV replication in vitro.

5' Untranslated Regions↗
PubMed2002

A humanized, nondepleting anti-CD4 antibody that blocks virus entry inhibits virus replication in rhesus monkeys chronically infected with simian immunodeficiency virus.

Therapeutic approaches that interfere with viral entry hold promise in preventing or treating HIV infection. Hu5A8, a humanized monoclonal antibody against CD4, was previously shown to inhibit HIV and SIV replication in vitro and was safely administered to rhesus monkeys without depleting CD4(+) T cells. This antibody completely suppressed replication of six different SIVmac 251 primary isolates in vitro. Twice weekly administration of 3-mg/kg doses of hu5A8 for 2 to 4 weeks to SIV-infected rhesus monkeys resulted in sustained plasma antibody levels of > or =20 microg/ml during treatment and 5- to 50-fold decreases in plasma viremia, although suppression of viral replication was transient. Two of three treated monkeys developed antibody responses against the administered monoclonal antibody. Loss of antiviral effect was not temporally associated with anti-hu5A8 antibody responses or due to activation of CD4(+) T cells by hu5A8. However, SIV isolated after hu5A8 treatment was approximately 5-fold more resistant to suppression by hu5A8 than SIV isolates obtained from the same monkeys before treatment. The rapid development of resistance may have resulted from SIV variants that infect cells by a CD4-independent mechanism. These results support the overall concept of anti-CD4 monoclonal antibody treatment to suppress AIDS virus replication in vivo while demonstrating important issues as to its clinical feasibility.

Animals↗
PubMed1999

Differential patterns of interaction between HIV type 1 and HTLV type I in monocyte-derived macrophages cultured in vitro: implications for in vivo coinfection with HIV type 1 and HTLV type I.

The interaction between human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia-lymphoma virus type I (HTLV-I) has generated substantial interest. However, there is disagreement on the in vivo consequences of the double infection. We investigated the interactions between HIV-1 and HTLV-I in monocyte-derived macrophages cultured in vitro. For study, the T cell-tropic strain IIIB and the macrophagetropic strain Ada-M of HIV-1 were used. The HTLV-I was prepared from the supernatants of the virus-producing MT-2 cell line. We found that coinfection of macrophages with T cell-tropic HIV-1 and HTLV-I significantly enhanced HIV-1 replication, whereas double infection of the cells with macrophage-tropic HIV-1 and HTLV-I resulted in marked upregulation of HTLV-I production. Stimulatory interactions between HIV-1 and HTLV-I were mediated by their trans-acting proteins. Results of study on nuclear translocation of proviral DNA showed that the tax gene product of HTLV-I was able to facilitate the nuclear import of the reverse-transcribed HIV-1(IIIB) DNA. In contrast, the HIV-1 Tat protein did not increase the intranuclear trafficking of HTLV-I DNA, which suggests another mechanism for HTLV-I enhancement by the tat gene product. In conclusion, this study provides possible mechanisms whereby coinfection of an individual with HIV-1 and HTLV-I may influence the clinical outcome of double infection.

Cell Nucleus↗
PubMed2000

Lentivirus vector mobilization and spread by human immunodeficiency virus.

The rapid advancement of lentivirus-based gene transfer systems and their demonstrated utility in a variety of in vitro and in vivo settings has heightened the need for assays to evaluate the safety of these vectors prior to human clinical trials. Two major concerns relating to the use of lentivirus-based vectors in a clinical setting are the presence of contaminating replication-competent retroviruses in vector preparations and the efficiency of vector mobilization and spread by wild-type helper virus (rescue). This article describes an in vitro system to study the rescue of lentivirus-based vectors by wild-type HIV. We show that lentivirus-based vectors can be readily rescued from T cell lines and to a lesser extent from primary human lymphocytes by wildtype HIV, resulting in the spread of mobilized vector particles to previously untransduced cells. Furthermore, we show that vector mobilization can be prevented by antiretroviral drugs such as AZT. In contrast to recently published reports by Bukovsky et al. and An et al., the lentivirus vectors used in these studies had little or no effect on the replication and spread of HIV in transduced cells [Bukovsky et al. (1999). J. Virol. 73, 7087-7092; An et al. (1999). J. Virol. 73, 7671-7677]. Whereas vector spread is a significant concern for most gene therapy applications, in the context of gene therapy for HIV infection it may have beneficial effects.

Cells, Cultured↗
PubMed2001

Approaches to gene therapy for human immunodeficiency virus infection.

Much progress has been made in developing new and more efficient treatments for human immunodeficiency virus (HIV) infection, the cause of acquired immunodeficiency syndrome (AIDS). However, the scope of the HIV epidemic and the limitations of existing treatments necessitate the continued development of novel treatment strategies. Gene therapy is one such forward-looking strategy. Gene therapy approaches for HIV infection include efforts to interfere with viral replication directly by engineering HIV-resistant cells or indirectly by eliminating infected cells from the body, primarily by eliciting a therapeutic immune response to destroy HIV-infected cells. Although the prospect of gene therapy as a routine treatment for HIV infection remains distant, continuous progress is being made, which should also have implications for gene therapy strategies for a variety of other diseases. This article reviews some of the strategies for investigating the feasibility of gene transfer for the treatment of HIV infection.

Animals↗
PubMed1990

Immunology of HIV infection, I: Biology of the interferons.

Interferons (IFN) are the prototypic biologic response modifiers. They comprise a multigene family of regulatory proteins and glycoproteins that affect a variety of cellular functions, including normal and neoplastic cell growth, immune reactivity, and host-parasite interactions. Their importance to basic cell biology and cellular immune defense, and their interactions with human immunodeficiency viruses (HIV) on the molecular and cellular levels, form the basis for this review.

HIV Infections↗
PubMed1986

Molecular cloning and expression in Escherichia coli of equine type I interferons.

Using human interferon-alpha 2 (IFN-alpha 2) and IFN-beta DNA to probe an equine genomic library we isolated recombinant phages containing genes for equine interferon-alpha (EqIFN-alpha), interferon-beta (EqIFN-beta), and interferon-omega (EqIFN-omega). Sequence and hybridization analyses of these genes reveal that the equine genome contains gene families of each of these three type I interferon classes. The mature proteins of EqIFN-alpha are 71-77% homologous to human IFN-alpha polypeptides, and, when expressed in E. coli, possess antiviral activity on both equine and human cells. By contrast, EqIFN-beta is only 59% homologous to its human counterpart and shows activity only on equine cells.

Animals↗
PubMed2005

Characterization of human immunodeficiency virus (HIV)-2 vector mobilization by HIV-1.

Conditionally replicating human immunodeficiency virus type 2 (crHIV-2) vectors can compete with HIV-1 for packaging in HIV-1-infected cells, indicating that the mobilization of vectors could selectively target as well as protect reservoirs susceptible to HIV-1 infection. The incorporation of HIV-1-specific antiviral transgenes in crHIV-2 vectors, although increasing the direct antiviral effect, may decrease mobilization and transmission to surrounding cells. To investigate how HIV-1-specific catalytic RNA cassettes (ribozymes) affect this balance between antiviral activity and mobilization, crHIV-2 vectors shown to display anti-HIV-1 activity were packaged by HIV-2 and used to transduce cells previously infected with HIV-1 or to transduce uninfected cells that were subsequently challenged with HIV-1. Vector mobilization was greater when HIV-1-infected cells were transduced with vector than when transduced cells were infected with HIV-1, and approximately 3-fold lower vector production was observed in cultures transduced with vectors expressing anti-HIV-1 ribozymes. Vector and antiviral effects could be transferred to new cultures by passaging supernatants to fresh cultures. No evidence of recombination with HIV-1 was observed. Vector mobilization and protection from HIV-1 infection were also demonstrated in human peripheral blood mononuclear cells. These data suggest that strategies employing vector mobilization for HIV-1 gene therapy should use vectors with maximal antiviral potency, despite resulting reductions in mobilization of the vector.

Base Sequence↗
PubMed2005

Potent antitumor activity of oncolytic adenovirus expressing mda-7/IL-24 for colorectal cancer.

It has been demonstrated that interleukin 24 (IL-24, also called melanoma differentiation associated gene 7) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirus-mediated gene transfer of IL-24 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-24 (ZD55-IL-24) was constructed by insertion of an IL-24 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. ZD55-IL-24 could express substantially more IL-24 than Ad-IL-24 because of replication of the vector. It has been shown that ZD55-IL-24 exerted a strong cytopathic effect and significant apoptosis in tumor cells with p53 dysfunction. Moreover, no cytotoxic and apoptotic effects could be seen in normal cells infected with ZD55-IL-24. Expression of IL-24 did not interfere with viral replication induced by oncolytic adenovirus. Activation of caspase 3 and caspase 9, and induction of bax gene expression, were involved in tumor cell apoptosis induced by ZD55-IL-24. Treatment of established tumors with ZD55-IL-24 showed much stronger antitumor activity than that induced by ONYX-015 or Ad-IL- 24. These data indicated that oncolytic adenovirus expressing IL-24 could exert potential antitumor activity and offer a novel approach to cancer therapy.

Adenoviridae↗
PubMed1983

Mouse monoclonal antibody with specificity for human interferon gamma.

We developed a monoclonal antibody (MAb) specific for human interferon gamma (HuIFN-gamma) by hybridizing cells from the NS-1 myeloma cell line with spleen lymphocytes from BALB/c mice immunized with partially purified HuIFN-gamma. Hybridoma culture supernatants were screened for neutralization of antiviral activity of HuIFN-gamma by the method determining the inhibition of nucleic acid synthesis assay (INAS), employing human fibroblasts infected with encephalomyocarditis virus (EMC). Clones exhibiting neutralization of antiviral activity of HuIFN-gamma were recloned, retested and an MAb with maximum neutralization activity was selected. This MAb was of IgM subclass and was specific for HuIFN-gamma. Antiviral activities either of human leukocyte-derived (HuIFN-alpha) or human fibroblast-derived interferon (HuIFN-beta) were not affected by this monoclonal antibody as determined by the INAS test. The specificity of the MAb for HuIFN-gamma was further confirmed by an indirect immunoprecipitation method, where monoclonal antibody-HuIFN-gamma complexes were immunoprecipitated with rabbit anti-mouse immunoglobulin and remaining IFN activity in the supernatants was determined by virus yield reduction assay. Ammonium sulfate precipitated preparations of this MAb were able to significantly increase (range of 230- to 1300-fold) the virus yield when compared with that obtained in the presence of IFN-gamma. SDS-PAGE analysis revealed that the MAb immunoprecipitates a molecule of Mr = 47 kD under nonreducing conditions. Under reducing conditions, two additional bands of Mr = 26 kD (major band) and Mr = 21 kD (minor band) were observed. A sepharose affinity column was constructed using this MAb and was able to retain approximately 60% of the partially purified HuIFN-gamma preparation applied. Significant amounts of HuIFN-gamma were eluted by increasing the ionic strength and decreasing the pH. HuIFN-alpha and HuIFN-beta were not retained by this column.

Animals↗
PubMed1980

Platelet-derived growth factor (PDGF) inhibits antiviral and anticellular actin of interferon in synchronized mouse or human cells.

Antiviral and anticellular action of purified mouse or human interferon was found to be inhibited in the quiescent, monolayer cultures of mouse or human fibroblasts (3T3 and FS-14) stimulated for growth by PDGF. In the asynchronous cell cultures the antagonistic effect of PDGF towards interferon, was much less evident. The optimal synchronization of cells for division was obtained by density inhibition and the incubation of the confluent cell monolayers in the low serum medium for 24 h and in 5% platelet poor plasma serum (PPPS) medium for further 24 h at 37 degrees C. Under appropriate conditions also pure epidermal growth factor (EGF) and fibroblast growth factor (FGF) acted as antagonists of interferon. It is suggested that interferons and growth factors are two families of hormones. The effects induced by interferons and growth factors are found to be directly opposite.

Animals↗
PubMed1981

Effect of anti-interferon serum on Friend virus infection and Fv-1-mediated resistance.

The purpose of these studies was (1) the quantitation of the protective effect of endogenous interferon (IFN) in the Friend virus (FV) system, and (2) the determination of the role of IFN in the relative resistance to FV mediated by the Fv-1-gene. In these studies, mice from two strains differing with respect to their Fv-1 alleles were treated with sheep anti-mouse IFN serum immediately prior to infection with N-tropic FV. The effect of this pretreatment showed that the neutralization of FV-induced IFN by anti-IFN resulted in a two to tenfold increase in susceptibility to FV infection as measured by the appearance of macroscopic foci of erythroleukemic cells on the splenic surface as compared to control mice which received normal sheep serum. At higher virus doses, an increase in spleen weight in anti-IFN-treated mice was also observed. Mice resistant to FV by virtue of their Fv-1 allele were affected by anti-IFN pretreatment only as much as mice from the susceptible strain. Therefore, IFN appeared to play no role in Fv-1-mediated resistance.

Animals↗
PubMed1981

Selection and characterization of virus-resistant L cell mutants with changed interferon gene expression.

A study was carried out on the relationship between the antiviral behaviour and changes in interferon (IFN) gene expression of virus-resistant cell mutants. Three virus-resistant L cell mutants were selected by mutagen-selection method. These mutant cell lines were found to show marked changes in their behaviour in both IFN induction and IFN action systems. An accelerated IFN induction response was observed in mutant cell cultures when they were exposed to NDV. Induced mutant cells synthesized IFN mRNA more quickly, and the IFN titers after induction with poly I:C were higher in mutant cell lines than those in the parent cell line. The virus-resistant L cell mutants appeared to be more sensitive to the anticell-division activity caused by ppp A2'p5'A2'p5'A. The results obtained suggest that changes in IFN gene expression may account for the antiviral behaviour of these cell mutants.

Animals↗
PubMed1982

Regulation of susceptibility to natural killer cells' cytotoxicity and regulation of HLA synthesis: differing efficacies of alpha, beta, and gamma interferons.

Interferon (IFN) is an effective activator of the natural killer (NK) cells but can also induce, in a variety of target cells, resistance to the NK induced cytolysis. We have compared the ability of the various types of human IFN to carry out this function, by quantitating the cytolysis induced by NK cells in cultured fibroblasts pretreated with each IFN and comparing this effect of the IFNs to their effectivity in suppressing viral replication. Relative to their antiviral potency, preparations of IFN-gamma were significantly more effective than the alpha or beta interferons in inducing what we call the "anti-NK" effect. Significant inhibition of the natural killing was observed with IFN-gamma even at concentrations at which no antiviral effect was induced. Preparations of IFN-gamma were also more effective than the other interferons in suppressing cell growth. While the induction of the enzyme oligo-isoadenylate synthetase correlated to the antiviral effectivity of the interferons, the quantitation of the HLA proteins in the cells had shown that their induction by the interferons correlates to the induction of the anti-NK effect, being stimulated much more effectively by IFN-gamma than by IFN-alpha or IFN-beta. The anti-NK, HLA and antiviral-inducing activities co-purified in fractionation of IFN-gamma preparations. These findings suggest the existence of several independent mechanisms for the regulation of cell functions by interferons. The gamma IFN is particularly effective in regulating functions involved in the interaction of cells with the immune system while the gamma virus-induced IFN-alpha and -beta are more effective as inducers of resistance to viral growth.

Cells, Cultured↗