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At least 991 records · Page 55Linked to original sources

PubMed1997

Booster immunization with a partially purified citrus tristeza virus (CTV) preparation after priming with recombinant CTV coat protein enhances the binding capacity of capture antibodies by ELISA.

Groups of rabbits and young lambs were immunized subcutaneously and intramuscularly with a recombinant citrus tristeza virus (CTV) coat protein (rCTV-CP) antigen. Three weeks after primary immunization the animals were divided into two groups that were boosted either with rCTV-CP or with a partially purified preparation of CTV particles (ppCTV). Twelve and 15 days after the last injection, the animals were bled and the binding capacity of the antisera for CTV detection was examined for capture antibodies by the indirect ELISA. Considerably higher ELISA titers were obtained from animals that were boosted with ppCTV than with rCP. Boosting with partially purified native antigens after priming with recombinant antigens is expected to extend the applicability of the antisera for detecting other structural and non-structural viral antigens by trapping ELISA.

Animals↗

PubMed2003

Inactivated Hantaan virus vaccine derived from suspension culture of Vero cells.

We have developed a cell culture-derived, inactivated vaccine against Hantaan virus for prevention of the hemorrhagic fever with renal syndrome (HFRS). Hantaan virus was purified from a microcarrier culture of Vero E6 cells by ultrafiltration and density gradient centrifugation. Viral infection was inactivated by treatment of the viral stock with formaldehyde. Immunogenic properties of the vaccine were characterized in comparison with Hantavax, a mouse brain-derived, formalin-inactivated vaccine that has been in human use for a decade in Korea. Compared to the Hantavax, immunization of Balb/c mice with the cell culture-based vaccine resulted in a moderate difference in antibody response to the viral nucleocapsid protein but more than five-fold increase in neutralizing activity. Moreover, all six mice immunized with 5 microg of the cell culture-based vaccine were fully protected from challenge with infectious virus, whereas virus was detected in lung and spleen of all animals immunized with the same dose of Hantavax. Four times higher dose of the latter vaccine was needed for complete protection. In the analysis of the humoral immune response to the vaccines, we found that all three viral structural proteins, N, G1 and G2 were immunoprecipitated by sera from animals immunized with the cell culture-based vaccine. In contrast, N and some G1 but no G2 were precipitated by the sera from animals immunized with Hantavax. These results suggest that the cell culture-based vaccine can provide more effective immunity than the Hantavax.

Animals↗

PubMed1998

Hepatitis B: virus, pathogenesis and treatment.

The hepatitis B virus (HBV) is a coated, incompletely double-stranded DNA virus with some outstanding features. (1) All three coat proteins of HBV contain HBsAg, which is highly immunogenic inducing anti-HBs. These antibodies are protective for HBV outer cells (humoural immunity). Structural viral proteins induce specific T-lymphocytes, which are able to eliminate HBV-infected cells (cytotoxic T-cells; cellular immunity). (2) Intracellular HBV primarily causes little or no damage (non-cytopathogenic), which is an excellent strategy of viral survival. However, viral oligo-peptides of 8-15 amino acids are loaded on host cell MHC-class 1 molecules and are transported to the cell surface. Thus, HBV-specific T-lymphocytes are able to detect infected cells and destroy them, an ingenious defence strategy. However, this cell deletion triggered by inflammation cells may result in acute hepatitis. If HBV is not eliminated, a delicate balance between viral replication and immunodefence prevails which may lead to chronic hepatitis and liver cirrhosis. (3) In chronically infected cells HBV may become partly cytopathogenic--a process still poorly understood--and the viral DNA may integrate into the host cell DNA (through a viral transcriptase). If integration leads to activation of crucial host genes a hepatocellular carcinoma results. These outstanding features are responsible for the highly variable course of HBV infection and its final outcome, e.g. when the load of HBV-infected cells is still low at the time when an efficient immune defence starts, the infection is self-limited and asymptomatic, and immunity results. When there is no immune defence or a defective immune defence (immune tolerance of new-borns or immunosuppressed individuals) the HBV infection very often becomes chronic. In these cases, no acute hepatitis occurs, but hepatocellular carcinoma may result. Treatment with Interferon has become accepted, resulting in up to 30 to 40% of cases in the elimination of the virus. However, treatment is laborious and expensive, and the mechanism of action is still poorly understood (anti-viral and/or immune-modulating).

Animals↗

PubMedDate not supplied

Scrapie infectious agent is virus-like in size and susceptibility to inactivation.

The virions of all known viruses are composed of small amounts of genomic nucleic acid enveloped by proteins and other macromolecules. The aetiological agents of scrapie disease and the other subacute spongiform virus encephalopathies (SSVE), a group of slow, fatal degenerative diseases of the central nervous system, are, based on their resistance to sterilization and on indirect measurements suggesting subviral size, thought to have non-viral structures (see refs 1-3 for reviews). The kinetic studies reported here demonstrate that scrapie's resistance to many inactivants is limited to small subpopulations of the total infectivity, the majority population being highly sensitive to inactivation. Moreover, control inactivations of conventional viruses provide examples of both scrapie-like resistant subpopulations and complete insensitivity to virucidal agents, especially when those viruses, like scrapie, are suspended in hamster brain homogenate. Virus controls further establish that the ability of the scrapie agent to penetrate dilute agarose-acrylamide electrophoretic gels is shared by conventional viruses. Direct comparison of scrapie's resistance to ionizing radiation with the resistances of other viruses places scrapie with the smaller viruses, as opposed to requiring a subviral size as claimed.

Animals↗

PubMed1995

A picornaviral protein synthesized out of frame with the polyprotein plays a key role in a virus-induced immune-mediated demyelinating disease.

The DA strain and other members of the TO subgroup of Theiler's murine encephalomyelitis virus (TMEV) induce a chronic demyelinating disease with a restricted virus expression. This disease serves as an experimental model of multiple sclerosis; in both diseases the immune system contributes to a similar demyelinating pathology. Like all picornaviruses, TMEV encodes a polyprotein translated from one long open reading frame. The polyprotein is then processed into structural and non-structural viral proteins. Here, we demonstrate that the DA strain of TMEV has an additional alternative open reading frame that encodes a protein called L* that is present in infected cells. Virus with a mutation of L* has a dramatically decreased demyelinating activity, indicating that L* plays a critical role in TO subgroup-induced demyelinating disease. L* is associated with membranes, suggesting that L* may interact with the immune system and thereby mediate the viral-induced demyelinating disease.

Animals↗

PubMed2003

Physical and functional interaction between HCV core protein and the different p73 isoforms.

Hepatitis C virus (HCV) core protein is a structural viral protein that packages the viral genomic RNA. In addition to this function, HCV core also modulates a number of cellular regulatory functions. In fact, HCV core protein has been found to modulate the expression of the cyclin-dependent inhibitor p21(WAF1/CIP1) and to promote both apoptosis and cell proliferation through its physical interaction with p53. Here, we studied the ability of HCV core to bind the p53-related p73 protein, its isoforms and its deletion mutants. We found that HCV core co-immunoprecipitated with p73 in HepG2 and SAOS-2 cells. Deletion mutational analysis of p73 indicates that the domain involved in HCV core binding is located between amino-acid residues 321-353. We also demonstrate that p73/core interaction results in the nuclear translocation of HCV core protein either in the presence of the p73 alpha or p73 beta tumor-suppressor proteins. In addition, the interaction with HCV core protein prevents p73 alpha, but not p73 beta dependent cell growth arrest in a p53-dependent manner. Our findings demonstrate that HCV core protein may directly influence the various p73 functions, thus playing a role in HCV pathogenesis.

Active Transport, Cell Nucleus↗

PubMed2003

White spot syndrome virus infection in cultured Penaeus vannamei (Boone) in Ecuador with emphasis on histopathology and ultrastructure.

Mortalities of cultured shrimp, Penaeus vannamei (Boone), induced by white spot syndrome virus (WSSV) have occurred in Ecuador since May 1999. Three epidemiological surveys in Ecuadorian farms were carried out and showed an apparent association between lower temperature and increased mortality rates in commercial ponds. Infected animals showed a reddish discolouration and lethargy and occasionally, white spots in the exoskeleton. Histopathological studies revealed that infected cells presented nuclear hypertrophy with eosinophilic to basophilic inclusions. In some cases, two other pathologies were observed: (a) lymphoid organ spheroids and (b) cells with pyknotic and karyorrhectic nuclei in the lymphoid organ, haematopoietic tissue, connective tissue, heart and antennal gland. Occasionally pyknotic cells were encapsulated without apparent injury to the adjacent tissue and without melanization. Transmission electron microscopy showed the presence of WSSV particles in the cytoplasm of cells with pyknotic nuclei in the stomach hypodermis. Viral structure and morphogenesis agreed with previous descriptions by other authors in WSSV-infected shrimp. Occasionally, two nucleocapsids within one envelope were present amongst single enveloped nucleocapsids. A long rod-shaped structure that could reach 2.4 microm in length was present in the nuclei of some infected cells.

Animals↗

PubMed1977

Cleavage of Rous sarcoma viral polypeptide precursor into internal structural proteins in vitro involves viral protein p15.

The polypeptide precursor pr76 to the internal viral group specific (gs) antigen proteins of Rous sarcoma virus, synthesized in a cell-free system of ascites cells, has been processed in vitro into the viral proteins by purified viral protein p15 as well as by disrupted Rous sarcoma virus. Disrupted Rauscher murine leukemia virus does not stimulate the cleavage process in vitro. Autocatalytic cleavage of the polypeptide precursor pr76 or Rous sarcoma virus, which contains the peptide sequence of p15, is not observed.

Antigens, Viral↗

PubMed1981

Induction of high serum levels of retroviral env gene products (gp70) in mice by bacterial lipopolysaccharide.

In the present study, mice each given a single intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS) responded with increased serum levels of the major envelope glycoprotein, gp70, of endogenous retrovirus. Concentrations of gp70 in their sera began to increase 4 hr after LPS injection, reached maximal 5- to 15-fold increases after 12--24 hr, and returned to the preinjection levels within 3 days. This response occurred only in the strains characterized by high base line levels of serum gp70 (greater than 10 micrograms/ml) such as NZB, NZB X NZW F1, BXSB, MRL, NZW, DBA/2, LG, 129(GIX+), and C57BL/6(GIX+). However, strains such as DBA/1, C3H/St, BALB/c, C57BL/6(GIX-), and 129(GIX-) with lower base line levels of serum gp70 (less than 5 micrograms/ml) made little or no response. This serum gp70 induced by LPS was structurally similar to the gp70 of NZB xenotropic virus that is dominantly expressed in sera from virtually all strains of mice. However, (i) the induced gp70 was virion-free; (ii) xenotropic virus was not isolatable from BXSB, MRL/1, or 129(GIX+) mice injected with LPS; and (iii) amounts of the major structural viral protein, p30, did not increase correspondingly in sera. All of these findings indicate that the increased expression of serum xenotropic viral gp70 in response to LPS did not result from activation of replication-competent xenotropic virus. In addition, the serum gp70 response to LPS was abolished by simultaneous inoculation of an inhibitor of protein synthesis, D-galactosamine. These results strongly suggest that LPS selectively stimulates synthesis of the env gene product, gp70, of NZB xenotropic virus but other viral gene products.

Animals↗

PubMed1989

v-src induces clonal sarcomas and rapid metastasis following transduction with a replication-defective retrovirus.

v-src is an effective carcinogen when expressed from Rous sarcoma virus (RSV) in vivo. Whereas RSV tumors require sustained oncogene expression, their growth is largely a balance between viral recruitment of tissues and host immune destruction of infected cells. We have therefore examined the tumorigenic potential of v-src in the absence of viral recruitment and viral antigen expression. v-src was introduced with high efficiency into chicken wing web tissues using replication-defective (rd) retroviral vectors. Clonal sarcomas were induced rapidly, and, furthermore, v-src potentiated metastatic progression in approximately 0.1%-1% of tumor clones with unexpectedly short latency. rd vectors proved effective not only in transducing v-src into tissues but also as insertional markers of tumor clonality. The rd vector present in most primary and metastatic tumors was a highly truncated form of RSV derived by viral transmission of spliced v-src mRNA; this vector should thus avoid viral recruitment and host anti-viral immune reaction through its complete lack of viral structural genes. Under such conditions v-src maintains strong carcinogenicity in vivo when restricted to clonal tumor growth and can confer rapid metastatic potential on a discrete subset of tumor clones.

Animals↗

PubMed2006

Isolation and molecular characterization of a new Muscovy duck parvovirus from Muscovy ducks in the USA.

Between 1997 and 1999 several cases of a new disease in Muscovy ducks were reported in Pennsylvania, USA. The cases were characterized by locomotor dysfunction, weakness, recumbency, 40 to 60% morbidity and 10 to 40% mortality. The most characteristic microscopic lesions were moderate to severe degenerative rhabodomyopathy. In order to characterize the aetiological agent, virus isolation was attempted from the spleen, liver, heart, skeletal muscle and intestine by inoculation of 14-day-old Muscovy duck embryos with tissue homogenates. Deaths occurred on the second egg passage and parvoviruses were isolated by serial passage of allantoic fluid from dead embryos and then in Muscovy duck embryo fibroblast (MDEF) cultures. Parvovirus particles were observed in allantoic fluids and supernatants of MDEF cultures by transmission electron microscopy. Two genomic fragments, comprising 1108 nucleotides of the right open reading frame that codes for the structural viral proteins 1, 2 and 3, were amplified by polymerase chain reaction from one of the isolates, Muscovy duck parvovirus (MDPV)/PSU-31010. Comparison of this fragment with available sequences of other MDPV and related goose parvovirus (GPV) isolates showed that it had only 84.5% sequence identity with other MDPV isolates and 84.6% identity with the GPV isolates. This region shares over 99% identity among previously sequenced MDPV isolates and 95% identity among the related GPV isolates. This suggests that MDPV/PSU-31010 is divergent from all other sequenced MDPV and GPV isolates, and may represent a new group of avian parvoviruses.

Amino Acid Sequence↗

PubMedDate not supplied

Antigenic and adjuvant activities of branched aliphatic oligoester (M-DL-LA) microspheres with incorporated bovine rotavirus.

Branched aliphatic oligoester microspheres (msp) with incorporated rotavirus were used to induce the production of systemic and mucosal antibodies in mice. The msp with a mean diameter of 7.4 microm were prepared by the w/o/w technique. The mice were immunized intraperitoneally or orally. High ELISA titres of systemic and local IgG and IgA antibodies were indicative of rotavirus incorporation and of the adjuvant activity of msp. Oral immunization with a split dose administered on three consecutive days, resulted in the production of systemic IgG and IgA antibodies, but failed to induce the production of mucosal antibodies even if the immunization dose was increased threefold. Specific antibodies were detectable in faeces of orally immunized mice only after another triple administration of the same dose in the fourth week of the experiment. Reactions of blood serum IgG with the structural viral proteins VP4, VP6, and VP7 were demonstrated by western blotting. Both systemic, and faecal IgA antibodies were specific for the VP6 protein and the dimeric form of the glycoprotein VP4.

Adjuvants, Immunologic↗

PubMedDate not supplied

Alphavirus replicon particles as candidate HIV vaccines.

Replicon particles based on Venezuelan equine encephalitis virus (VEE) contain a self-replicating RNA encoding the VEE replicase proteins and expressing a gene of interest in place of the viral structural protein genes. Structural proteins for packaging of replicon RNA into VEE replicon particles (VRPs) are expressed from separate helper RNAs. Aspects of the biology of VEE that are exploited in VRP vaccines include 1) expression of very high levels of immunogen, 2) expression of immunizing proteins in cells in the draining lymph node, and 3) the ability to induce mucosal immunity from a parental inoculation. Results of experiments with VRPs expressing green fluorescent protein or influenza virus hemagglutinin (HA) demonstrated that specific mutations in the VRP envelope glycoproteins affect both targeting in the draining lymph node and efficiency of the immune response in mice. VRPs expressing either the matrix-capsid portion of Gag, the full-length envelope gp160, or the secreted gp140 of cloned SIVsm H-4i were mixed in a cocktail and used to immunize macaques at 0, 1, and 4 months. Neutralizing antibodies against SIVsm H-4 were induced in 6 of 6 vaccinates and CTL in 4 of 6. An intrarectal challenge with the highly pathogenic SIVsm E660 was given at 5 months. A vaccine effect was seen in reduced peak virus loads, reduced virus loads both at set point and at 41 weeks postchallenge, and preserved or increased CD4 counts compared to controls. A candidate VRP HIV vaccine expressing Clade C Gag contains a sequence that is very close to the South African Clade C consensus and was selected from a recent seroconverter in the Durban cohort to represent currently circulating genotypes in South Africa. A GMP lot of this vaccine has been manufactured and tested for a phase I trial in the first months of 2002.

AIDS Vaccines↗

PubMed1977

In vitro generation of tumor-specific cytotoxic lymphocytes. Secondary allogeneic mixed tumor lymphocyte culture of normal murine spleen cells.

In vivo or in vitro immunity to murine leukemia virus (MuLV)-induced leukemia cells which do not effectively produce virus, has been difficult to demonstrate. Because immunizations with allogeneic murine leukemia cells have been used to confer syngeneic tumor immunity to virus- producing cells, we attempted to generate lymphocytes, cytotoxic to syngeneic nonproducer leukemia cells, by stimulating normal murine spleen cells with allogeneic nonproducer leukemia cells in mixed tumor lymphocyte culture (MTLC) reactions in vitro. Secondary allogeneic MTLC of normal C57BL/6 or DBA/2 spleen cells effectively produced syngeneic tumor-specific cytotoxic lymphocytes. Target cells lysed in lymphocyte- mediated cytolysis (LMC) assays, included both Friend and Rauscher virus- induced syngeneic murine leukemia cells and chemically-induced hematopoietic tumor cells. Syngeneic tumor cells were lysed regardless of whether they produced infectious MuLV or expressed viral antigens gp-71, p-30, or p-12 at the cell surface. Syngeneic normal cells (thymus, lymph node, or Concanavalin A-stimulated spleen cells) used as targets in LMC assays were uneffected by lymphocytes harvested from secondary allogeneic MTLC. Several other in vitro culture treatments including secondary syngeneic MTLC and repetitive mixed lymphocyte culture stimulations were incapable of generating tumor-specific cytotoxic lymphocytes. Based upon these results, we propose that secondary MTLC stimulation of normal spleen cells with allogeneic nonproducer leukemia cells selects for the proliferation of two subpopulations of antigen-specific cytotoxic lymphocytes. The population capable of effecting syngeneic tumor cell lysis is directed against tumor-associated cell surface antigens which may be distinct from viral structural proteins or glycoproteins. The growth of these tumor-specific cytotoxic lymphocytes may be enhanced by a soluble allogeneic effect factor produced by the proliferation of the second subpopulation of lymphocytes generated in repetitive allogeneic MTLC, namely those lymphocytes with specificities directed against differing histocompatibility antigens.

Animals↗

PubMed1994

HIV type 1 Tat protein induces immunoglobulin and interleukin 6 synthesis by uninfected peripheral blood mononuclear cells.

Tat is a potent trans-activating protein encoded by the HIV genome. It is essential for viral replication, but has pleiotropic effects on host cells as well. We demonstrated that exogenous recombinant Tat increases immunoglobulin (Ig) and interleukin 6 (IL-6) production in vitro by normal uninfected peripheral blood mononuclear cells by 100-500%. The optimal Tat concentration was 100 ng/ml, but even a low concentration of 1 ng/ml induced a response in most subjects. The observed induction was inhibited by monoclonal anti-Tat antibodies and 2,3-dimercapto-1-propanol. Both anti-IL-6 antibodies and IL-6 antisense oligonucleotides inhibited Tat-induced IgG and IgA synthesis to some degree, whereas induction of IgM appeared to be independent of IL-6. We conclude that Tat can function in vitro in the absence of any other viral structures and induce Ig and IL-6 production; the clinical significance of these findings remains as yet undetermined.

Adult↗

PubMed1998

Impairment of excitatory amino acid transport in astroglial cells infected with the human immunodeficiency virus type 1.

Perturbation of astrocyte functions by HIV-1 infection may contribute to the pathogenesis of AIDS dementia complex (ADC). The present study investigated the possibility that astroglial transport of glutamate and aspartate, the major excitatory amino acids (EAAs) in the mammalian central nervous system (CNS), is altered by HIV-1 infection. Human U251 glioma cells were infected with the brain isolate SF162 of HIV-1. HIV-1 persisted in glial cells over several months. This nonproductive infection of glial cells was characterized by persistent expression of Nef over the time of the infection, and the transient presence of structural viral proteins, including the viral transmembrane glycoprotein gp41, which was detected during the initial 2 weeks following HIV-1 infection. The presence of gp41 in acutely HIV-1-infected glial cells coincided with a 36% decrease in D-[3H]aspartate uptake, owing to a reduction in the maximal transport capacity (vmax) for D-aspartate. The expression of typical astrocytic glutamate transporters EAAT1 and EAAT2 in U251 glioma cells was not altered by HIV-1 infection. To determine whether viral protein gp120, gp41, or Nef was involved in the impairment of EAA transport in acutely HIV-1-infected glial cells, effects of lentiviral lytic peptide type 1 (LLP-1) (corresponding to the carboxy terminus of gp41), recombinant SF2 gp120, and recombinant LAI Nef on D-[3H]aspartate uptake and the release of glutamate in glial cells were investigated. Only LLP-1 reduced D-[3H]aspartate uptake and facilitated the release of glutamate from glial cells in a concentration-dependent manner. These results suggest that the carboxy terminus of gp41 impairs EAA transport in glial cells, which may contribute to excitotoxic damage to neurons in HIV-1 infection of the CNS.

Aspartic Acid↗

PubMed2001

Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 L1 virus-like particle vaccine.

BACKGROUND: Studies in animal models have shown that systemic immunization with a papillomavirus virus-like particle (VLP) vaccine composed of L1, a major structural viral protein, can confer protection against subsequent experimental challenge with the homologous virus. Here we report results of a double-blind, placebo-controlled, dose-escalation trial to evaluate the safety and immunogenicity of a human papillomavirus (HPV) type 16 (HPV16) L1 VLP vaccine in healthy adults. METHODS: Volunteers were given intramuscular injections with placebo or with 10- or 50-microg doses of HPV16 L1 VLP vaccine given without adjuvant or with alum or MF59 as adjuvants at 0, 1, and 4 months. All vaccine recipients were monitored for clinical signs and symptoms for 7 days after each inoculation. Immune responses were measured by an HPV16 L1 VLP-based enzyme-linked immunosorbent assay (ELISA) and by an HPV16 pseudovirion neutralization assay. The antibody titers were given as the reciprocals of the highest dilution showing positive reactivity in each assay. All statistical tests were two-sided. RESULTS: The prevaccination geometric mean ELISA titer for six seropositive individuals was 202 (range, 40--640). All vaccine formulations were well tolerated, and all subjects receiving vaccine seroconverted. Serum antibody responses at 1 month after the third injection were dose dependent in recipients of vaccine without adjuvant or with MF59 but were similar at both doses when alum was the adjuvant. With the higher dose, the geometric means of serum ELISA antibody titers (95% confidence intervals) to purified VLP 1 month after the third injection were as follows: 10,240 (1499 to 69 938) without adjuvant, 10,240 (1114 to 94 145) with MF59, and 2190 (838 to 5723) with alum. Responses of subjects within each group were similar. Neutralizing and ELISA antibody titers were highly correlated (Spearman correlation =.85), confirming that ELISA titers are valid proxies for neutralizing antibodies. CONCLUSIONS: The HPV16 L1 VLP vaccine is well tolerated and is highly immunogenic even without adjuvant, with the majority of the recipients achieving serum antibody titers that were approximately 40-fold higher than what is observed in natural infection.

Adjuvants, Immunologic↗

PubMed1983

The gene S promoter of hepatitis B virus confers constitutive gene expression.

The properties of the promoter of the hepatitis B surface antigen (HBsAg) were studied using recombinants containing either this promoter or the SV40 early promoter. Mouse L cells were transfected with these recombinants and the levels of gene expression obtained with the two promoters were compared. The level of expression of a cellular gene, the human fibroblast interferon gene, obtained with the HBsAg promoter was comparable to that obtained with the SV40 early promoter. Similarly when the HBsAg gene was controlled by the SV40 early promoter the level of HBsAg synthesis is in the same range as that observed with its own promoter. Together these results suggest that although the HBsAg gene codes for a structural viral protein, its expression is constitutive as for an early gene. The implications of these observations on the synthesis of HBV particles in vivo are discussed.

Animals↗