bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance to Friend Murine Leukemia Virus Infection Conferred by theFv-4Gene Is Recessive but Appears Dominant from the Effect of the Immune System
Authors: Zhang Fengmin , Ya Lamin Ta , Iwatani Yasumasa , Higo Kyoko , Suzuki Yasunori , Tanaka Masakazu , Nakahara Tomomi , Ono Takeshi , Sakai Hiroyuki , Kuribayashi Kagemasa , Ishimoto Akinori 
Published: July 2002

ABSTRACTFv-4is a mouse gene that dominantly confers resistance to infection with Friend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473–478, 1975). However, the resistance caused byFv-4is recessive in nude mice, which suggests that immunological effects play important roles in this resistance in vivo (K. Higo, Y. Kubo, Y. Iwatani, T. Ono, M. Maeda, H. Hiai, T. Masuda, K. Kuribayashi, F. Zhang, T. Lamin, A. Adachi, and A. Ishimoto, J. Virol. 71:750–754, 1997). To determine the immunological effect on the resistance in vivo, we infected immunologically immature newborn mice homozygous (Fv-4r/r) and heterozygous (Fv-4r/−) forFv-4. Although theFv-4r/rmice showed complete resistance to F-MuLV whether infected neonatally or as adolescents, theFv-4r/−mice showed high sensitivity to viral proliferation and disease induction when infected as newborns but complete resistance when infected as adolescent mice. To confirm the immunological effect on the resistance in adolescent mice with theFv-4r/randFv-4r/−genotypes, we examined the effect of an immunosuppressant drug, FK506, on the resistance. The mice with theFv-4r/rgenotype treated with FK506 still showed resistance, but the mice with theFv-4r/−genotype became highly sensitive to F-MuLV infection. Flow cytometric analysis to detect theFv-4gene product showed that theFv-4gene product was expressed on the cells from newborn and adolescent mice. TheFv-4gene product was also detected on the cells from the FK506-treated mice as well as on those from untreated mice. However, a quantitative difference in the gene product between the cells with theFv-4r/randFv-4r/−genotypes was detected by indirect staining for flow cytometry. These results show that the resistance to F-MuLV infection conferred by theFv-4gene is originally recessive, but it looks dominant in adolescent mice mainly because of the effect of the immune system.
Induction of Mucosal Homing Virus-Specific CD8+T Lymphocytes by Attenuated Simian Immunodeficiency Virus
Authors: Cromwell Mandy A. , Veazey Ronald S. , Altman John D. , Mansfield Keith G. , Glickman Rhona , Allen Todd M. , Watkins David I. , Lackner Andrew A. , Johnson R. Paul 
Published: July 2002

ABSTRACTInduction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8+lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor α4β7 and traffic to the intestinal mucosa. SIV-specific CD8+T cells expressing α4β7 were detected in peripheral blood and intestine of macaques infected with attenuated SIV. In contrast, virus-specific T cells in blood of animals immunized cutaneously by a combined DNA-modified vaccinia virus Ankara regimen did not express α4β7. These results demonstrate the selective induction of SIV-specific CD8+T lymphocytes expressing α4β7 by a vaccine approach that replicates in mucosal tissue and suggest that induction of virus-specific lymphocytes that are able to home to mucosal sites may be an important characteristic of a successful AIDS vaccine.
Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIV
Authors: Ourmanov Ilnour , Brown Charles R. , Moss Bernard , Carroll Miles , Wyatt Linda , Pletneva Liuobov , Goldstein Simoy , Venzon David , Hirsch Vanessa M. 
Published: July 2002

ABSTRACTPrior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al., J. Virol. 70:3741–3752, 1996). This MVA-SIV recombinant expressed relatively low levels of the Gag-Pol portion of the vaccine. To optimize protection, second-generation recombinant MVAs that expressed high levels of either Gag-Pol (MVA-gag-pol) or Env (MVA-env), alone or in combination (MVA-gag-pol-env), were generated. A cohort of 24 macaques was immunized with recombinant or nonrecombinant MVA (four groups of six animals) and was challenged with 50 times the dose at which 50% of macaques are infected with uncloned pathogenic SIVsmE660. Although all animals became infected postchallenge, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines as compared with animals that received nonrecombinant MVA (P= 0.0011 by repeated-measures analysis of variance). The differences in the degree of virus suppression achieved by the three MVA-SIV vaccines were not significant. Most importantly, the reduction in levels of viremia resulted in a significant increase in median (P< 0.05 by Student'sttest) and cumulative (P= 0.010 by log rank test) survival. These results suggest that recombinant MVA has considerable potential as a vaccine vector for human AIDS.
Herpes Simplex Virus ICP27 Induces Cytoplasmic Accumulation of Unspliced Polyadenylated α-Globin Pre-mRNA in Infected HeLa Cells
Authors: Cheung Peter , Ellison Kimberly S. , Verity Robert , Smiley James R. 
Published: July 2002

ABSTRACT
Transcripts of most intron-bearing cellular genes must be processed by the splicing machinery in order to efficiently accumulate and gain access to the cytoplasm. However, we found that herpes simplex virus induces cytoplasmic accumulation of both spliced and unspliced polyadenylated α-globin RNAs in infected HeLa cells. Accumulation of the unspliced RNA required the immediate-early protein ICP27, and ICP27 was sufficient (in combination with ICP4) to produce this effect in a transient-transfection assay. However, expression of ICP27 did not markedly alter the levels of fully spliced α-globin transcripts in infected cells. These data demonstrate that the previously documented effects of ICP27 on the cellular splicing apparatus do not greatly inhibit splicing of α-globin RNA and argue that ICP27 induces a splicing-independent pathway for α-globin RNA accumulation and nuclear export.
Virus Load and Sequence Variation in Simian Retrovirus Type 2 Infection
Authors: Rosenblum Lisa L. , Weiss Robin A. , McClure Myra O. 
Published: July 2002

ABSTRACT

The natural history of type D simian retrovirus (SRV) infection is poorly characterized in terms of viral load, antibody status, and sequence variation. To investigate this, blood samples were taken from a small cohort of mostly asymptomatic cynomolgus macaques (
Macaca fascicularis
), naturally infected with SRV type 2 (SRV-2), some of which were followed over an 8-month period with blood taken every 2 months. Provirus and RNA virus loads were obtained, the samples were screened for presence of antibodies to SRV-2 and neutralizing antibody titers to SRV-2 were assayed.
env
sequences were aligned to determine intra- and intermonkey variation over time. Virus loads varied greatly among cohort individuals but, conversely, remained steady for each macaque over the 8-month period, regardless of their initial levels. No significant sequence variation was found within an individual over time. No clear picture emerged from these results, which indicate that the variables of SRV-2 infection are complex, differ from those for lentivirus infection, and are not distinctly related to disease outcome.
Defective Interfering RNAs of a Satellite Virus
Authors: Qiu Wenping , Karen-Beth Scholthof G. 
Published: July 2002

ABSTRACT

Panicum mosaic virus
(PMV) is a recently molecularly characterized RNA virus with the unique feature of supporting the replication of two subviral RNAs in a few species of the family
Gramineae
. The subviral agents include a satellite RNA (satRNA) that is devoid of a coding region and the unrelated satellite panicum mosaic virus (SPMV) that encodes its own capsid protein. Here we report the association of this complex with a new entity in the RNA world, a defective-interfering RNA (DI) of a satellite virus. The specificity of interactions governing this four-component viral system is illustrated by the ability of the SPMV DIs to strongly interfere with the accumulation of the parental SPMV. The SPMV DIs do not interfere with PMV satRNA, but they do slightly enhance the rate of spread and titer of PMV. The SPMV-derived DIs provide an additional avenue by which to investigate fundamental biological questions, including the evolution and interactions of infectious RNAs.
Comparison of Replication-Competent Molecular Clones of Porcine Endogenous Retrovirus Class A and Class B Derived from Pig and Human Cells
Authors: Krach Ulrich , Fischer Nicole , Czauderna Frank , Tönjes Ralf R. 
Published: July 2002

ABSTRACT

Vertically transmitted endogenous retroviruses pose an infectious risk in the course of pig-to-human transplantation of cells, tissues, and organs. Two classes of polytropic type C porcine endogenous retroviruses (PERV) which are infectious for human cells in vitro are known. Recently, we described the cloning and characterization of replication-competent PERV-B sequences from productively infected human cells (F. Czauderna, N. Fischer, K. Boller, R. Kurth, and R. R. Tönjes, J. Virol. 74:4028–4038, 2000). Here, we report the isolation of infectious molecular PERV-A and PERV-B clones from pig cells and compare these proviruses with clones derived from infected human 293 cells. In addition to clone PERV-A(42) derived from 293 cells, four “native” full-length proviral PERV sequences derived from a genomic library of the porcine cell line PK15 were isolated. Three identical class A clones, designated PK15-PERV-A(42), PK15-PERV-A(45), and PK15-PERV-A(58), and one class B clone, PK15-PERV-B(213), were characterized. PK15-PERV-B(213) is highly homologous but distinct from the previously described clone PERV-B(43). PK15-PERV-A(58) demonstrates close homology to PERV-A(42) in
env
and to PERV-C in long terminal repeat,
gag
, and
pro
/
pol
sequences. All three PERV clones described here were replication competent upon infection of susceptible cell lines. The findings suggest that the pig genome harbors a limited number of infectious PERV-A and -B sequences.
p21cip1 Degradation in Differentiated Keratinocytes Is Abrogated by Costabilization with Cyclin E Induced by Human Papillomavirus E7
Authors: Noya Francisco , Chien Wei-Ming , Broker Thomas R. , Chow Louise T. 
Published: July 2002

ABSTRACT
The human papillomavirus (HPV) E7 protein promotes S-phase reentry in a fraction of postmitotic, differentiated keratinocytes. Here we report that these cells contain an inherent mechanism that opposes E7-induced DNA replication. In organotypic raft cultures of primary human keratinocytes, neither cyclin E nor p21cip1 is detectable in situ. However, E7-transduced differentiated cells not in S phase accumulate abundant cyclin E and p21cip1. We show that normally p21cip1 protein is rapidly degraded by proteasomes. In the presence of E7 or E6/E7, p21cip1, cyclin E, and cyclin E2 proteins were all up-regulated. The accumulation of p21cip1 protein is a posttranscriptional event, and ectopic cyclin E expression was sufficient to trigger it. In constract, cdk2 and p27kip1 were abundant in normal differentiated cells and were not significantly affected by E7. Cyclin E, cdk2, and p21cip1 or p27kip1 formed complexes, and relatively little kinase activity was found associated with cyclin E or cdk2. In patient papillomas and E7 raft cultures, all p27kip1-positive cells were negative for bromodeoxyuridine (BrdU) incorporation, but only some also contained cyclin E and p21cip1. In contrast, all cyclin E-positive cells also contained p27kip1. When the expression of p21cip1 was reduced by rottlerin, a PKC δ inhibitor, p27kip1- and BrdU-positive cells remained unchanged. These observations show that high levels of endogenous p27kip1 can prevent E7-induced S-phase reentry. This inhibition then leads to the stabilization of cyclin E and p21cip1. Since efficient initiation of viral DNA replication requires cyclin E and cdk2, its inhibition accounts for heterogeneous viral activities in productively infected lesions.
Intrahepatic Genetic Inoculation of Hepatitis C Virus RNA Confers Cross-Protective Immunity
Authors: Weiner Amy J. , Paliard Xavier , Selby Mark J. , Medina-Selby Angelica , Coit Doris , Nguyen Steve , Kansopon Joe , Arian Christopher L. , Ng Philip , Tucker Jeffery , Lee Chun-Ting , Polakos Noelle K. , Han Jang , Wong Shirley , Lu Hui-Hua , Rosenberg Steve , Brasky Kathy M. , Chien David , Kuo George , Houghton Michael 
Published: July 2002

ABSTRACT
Naturally occurring hepatitis C virus (HCV) infection has long been thought to induce a weak immunity which is insufficient to protect an individual from subsequent infections and has cast doubt on the ability to develop effective vaccines. A series of intrahepatic genetic inoculations (IHGI) with type 1a HCV RNA were performed in a chimpanzee to determine whether a form of genetic immunization might stimulate protective immunity. We demonstrate that the chimpanzee not only developed protective immunity to the homologous type 1a RNA after rechallenge by IHGI but was also protected from chronic HCV infection after sequential rechallenge with 100 50% chimpanzee infectious doses of a heterologous type 1a (H77) and 1b (HC-J4) whole-virus inoculum. These results offer encouragement to pursue the development of HCV vaccines.
E1B 19K Blocks Bax Oligomerization and Tumor Necrosis Factor Alpha-Mediated Apoptosis
Authors: Sundararajan Ramya , White Eileen 
Published: July 2002

ABSTRACT
Tumor necrosis factor alpha (TNF-α)-mediated death signaling causes the recruitment of monomeric pro- apoptotic Bax into a 500-kDa protein complex. The adenovirus Bcl-2 homologue, E1B 19K, inhibits TNF-α-mediated apoptosis, interacts with Bax, and blocked the formation of the 500-kDa Bax complex. TNF-α and truncated Bid induced Bax-Bax cross-linking, indicative of oligomerization, and E1B 19K expression during infection inhibited this TNF-α-mediated Bax oligomerization. TNF-α signaled conformation changes at the Bax amino and carboxy termini. Exposure of the Bax amino terminus facilitates E1B 19K-Bax binding, which prevented exposure of the carboxy-terminal Bax Bcl-2 homology region 2 epitope. Inhibition of Bax oligomerization by E1B 19K is an activity that bears striking similarity to the means by which bacterial immunity proteins block pore formation by bacterial toxins which have structural homology to Bax.
Activation of NF-κB by the Human Herpesvirus 8 Chemokine Receptor ORF74: Evidence for a Paracrine Model of Kaposi's Sarcoma Pathogenesis
Authors: Pati Shibani , Cavrois Marielle , Guo Hong-Guang , Foulke James S. , Kim Jynho , Feldman Ricardo A. , Reitz Marvin 
Published: July 2002

ABSTRACTInfection with human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, is necessary for the development of KS. The HHV-8 lytic-phase gene ORF74 is related to G protein-coupled receptors, particularly interleukin-8 (IL-8) receptors. ORF74 activates the inositol phosphate/phospholipase C pathway and the downstream mitogen-activated protein kinases, JNK/SAPK and p38. We show here that ORF74 also activates NF-κB independent of ligand when expressed in KS-derived HHV-8-negative endothelial cells or primary vascular endothelial cells. NF-κB activation was enhanced by the chemokine GROα, but not by IL-8. Mutation of Val to Asp in the ORF74 second cytoplasmic loop did not affect ligand-independent signaling activity, but it greatly increased the response to GROα. ORF74 upregulated the expression of NF-κB-dependent inflammatory cytokines (RANTES, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor) and adhesion molecules (VCAM-1, ICAM-1, and E-selectin). Supernatants from transfected KS cells activated NF-κB signaling in untransfected cells and elicited the chemotaxis of monocytoid and T-lymphoid cells. Expression of ORF74 conferred on primary endothelial cells a morphology that was strikingly similar to that of spindle cells present in KS lesions. Taken together, these data, demonstrating that ORF74 activates NF-κB and induces the expression of proangiogenic and proinflammatory factors, suggest that expression of ORF74 in a minority of cells in KS lesions could influence uninfected cells or latently infected cells via autocrine and paracrine mechanisms, thereby contributing to KS pathogenesis.
Polymorphisms in HLA Class I Genes Associated with both Favorable Prognosis of Human Immunodeficiency Virus (HIV) Type 1 Infection and Positive Cytotoxic T-Lymphocyte Responses to ALVAC-HIV Recombinant Canarypox Vaccines
Authors: Kaslow Richard A. , Rivers Charles , Tang Jianming , Bender Thomas J. , Goepfert Paul A. , El Habib Raphaelle , Weinhold Kent , Mulligan Mark J. ,   the NIAID Aids Vaccine Evaluation Group
Published: July 2002

ABSTRACTCarriers of certain human leukocyte antigen class I alleles show favorable prognosis of human immunodeficiency virus type 1 (HIV-1) infection, presumably due to effective CD8+cytotoxic T-lymphocyte responses, but close relationships between class I variants mediating such responses to natural and to vaccine HIV-1 antigen have not been established. During 6 to 30 months of administration and follow-up in trials of ALVAC-HIV recombinant canarypox vaccines, cells from 42% of 291 HIV-1-negative vaccinated subjects typed at class I loci responded to an HIV-1 protein in a lytic bulk CD8+cytotoxic T-lymphocyte assay. By 2 weeks after the second dose, higher proportions of vaccinees carrying one of two alleles consistently associated with slower progression of natural HIV-1 infection reacted at least once: B∗27 carriers reacted to Gag (64%; odds ratio [OR] = 10.3,P= 0.001) and Env (36%; OR = 4.6,P= 0.04), and B∗57 carriers reacted to Env (44%; OR = 6.6,P< 0.05). By 2 weeks after the third or fourth dose, B∗27 carriers had responded (two or more reactions) to Gag (33%; OR = 4.4,P< 0.05) and B∗57 carriers had responded to both Gag (39%; OR = 5.3,P= 0.013) and Env (39%; OR = 9.5,P= 0.002). Homozygosity at class I loci, although conferring an unfavorable prognosis following natural infection, showed no such disadvantage for vaccine response. Individual class I alleles have not previously demonstrated such clear and consistent relationship with both the clinical course of an infection and cellular immunity to a vaccine against the infectious agent. This proof of principle that class I an alleles modulate both processes has implications for development of HIV-1 and presumably other vaccines.
Virus-Cell Interactions Regulating Induction of Tumor Necrosis Factor Alpha Production in Macrophages Infected with Herpes Simplex Virus
Authors: Paludan Søren R. , Mogensen Søren C. 
Published: July 2002

ABSTRACTMacrophages respond to virus infections by rapidly secreting proinflammatory cytokines, which play an important role in the first line of defense. Tumor necrosis factor alpha (TNF-α) is one of the major macrophage-produced cytokines. In this study we have investigated the virus-cell interactions responsible for induction of TNF-α expression in herpes simplex virus (HSV)-infected macrophages. Both HSV type 1 (HSV-1) and HSV-2 induced TNF-α expression in macrophages activated with gamma interferon (IFN-γ). This induction was to some extent sensitive to UV treatment of the virus. Virus particles unable to enter the cells displayed reduced capacity to stimulate TNF-α expression but retained a significant portion which was abolished by HSV-specific antibodies. Recombinant HSV-1 glycoprotein D was able to trigger TNF-α secretion in concert with IFN-γ. Sugar moieties of HSV glycoproteins have been reported to be involved in induction of IFN-α but did not contribute to TNF-α expression in macrophages. Moreover, the entry-dependent portion of the TNF-α induction was investigated with HSV-1 mutants and found to be independent of the tegument proteins VP16 and UL13 and partly dependent on nuclear translocation of the viral DNA. Finally, we found that macrophages expressing an inactive mutant of the double-stranded RNA (dsRNA)-activated protein kinase (PKR) produced less TNF-α in response to infectious HSV infection than the empty-vector control cell line but displayed the same responsiveness to UV-inactivated virus. These results indicate that HSV induces TNF-α expression in macrophages through mechanisms involving (i) viral glycoproteins, (ii) early postentry events occurring prior to nuclear translocation of viral DNA, and (iii) viral dsRNA-PKR.
Internal Ribosome Entry Site Regulates Translation of Kaposi's Sarcoma-Associated Herpesvirus FLICE Inhibitory Protein
Authors: Low Walter , Harries Mark , Ye Hongtao , Du Ming-Qing , Boshoff Chris , Collins Mary 
Published: July 2002

ABSTRACT
The gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) (or human herpesvirus 8) is associated with the endothelial tumor Kaposi's sarcoma (KS) and lymphoproliferative disorders in immunocompromised individuals. Only a small number of viral proteins are expressed in B cells latently infected with KSHV; here we characterize the mechanism of expression of one of these, the viral FLICE inhibitory protein v-FLIP (K13, ORF71). The v-FLIP coding region is present in a bicistronic message, following the v-cyclin coding region. Using both in vitro translation and cell transfection assays, we have identified an internal ribosome entry site (IRES) preceding the v-FLIP start codon and overlapping the v-cyclin (ORF 72) coding region, which allows v-FLIP translation. Using an antibody against v-FLIP we have detected expression of the endogenous protein in latently infected KSHV-positive primary effusion lymphoma (PEL) cell lines. Induction of apoptosis by serum withdrawal from PEL cells results in a relative increase in v-FLIP synthesis, as previously described for some cellular proteins translated from IRES.
JC Virus-Specific Cytotoxic T Lymphocytes in Individuals with Progressive Multifocal Leukoencephalopathy
Authors: Koralnik Igor J. , Du Pasquier Renaud A. , Letvin Norman L. 
Published: July 2002

ABSTRACTProgressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the polyomavirus JC (JCV) within a setting of immunosuppression. The nature of the immune response that contains replication of this virus is unknown. We have explored JCV-specific cellular immune responses in patients with PML and control subjects. JCV antigen-stimulated peripheral blood mononuclear cells (PBMC) of four human immunodeficiency virus (HIV)-infected patients who were survivors of PML and one HIV-uninfected patient recently diagnosed with PML lysed autologous B-lymphoblastoid cell lines expressing either the JCV T regulatory protein or the VP1 major capsid protein. This lysis was mediated by CD8+T lymphocytes and was major histocompatibility complex class I restricted. These cells were therefore cytotoxic T lymphocytes (CTL). JCV-specific CTL could not be detected in PBMC of three HIV-infected PML patients who had progressive neurologic disease and an eventual fatal outcome. These data suggest that the JCV-specific cellular immune response may play a crucial role in the containment of PML. This finding may also prove useful as a favorable prognostic marker in the clinical management of these patients.