Biomedical subjects

Y Becker

Publications and source records attributed to Y Becker.

At least 37 records · Page 2Linked to original sources

PubMed1995

Virus-neutralization domains on the oligomeric (230 kDa) forms of antigen B of herpesvirus of turkeys and Marek's disease virus differ in cross-serotypic activity.

Herpesvirus of turkeys (HVT) is frequently used to protect chickens against Marek's disease (MD). The HVT and MDV native antigen B complex shares common epitopes. To determine whether these oligomers present virus-neutralizing domains, monospecific antibodies to the HVT and MDV native 230 kDa oligomers were produced. The monospecific antibody immunopurified from an anti-HVT avian serum neutralized the in vitro infectivity of the oncogenic isolate MDV-B and the vaccine strains CVI988, SB1 and HVT and immunoblotted the 230 kDa oligomers of HVT and CVI988. As a result of the immunofluorescence analysis on infected cells, the monospecific antibody revealed foci of diffuse cytoplasmic immunofluorescence. A second monospecific antibody to the heat-stable 130 kDa monomer of HVT had limited neutralizing activity against HVT and CVI988 only, immunoblotted only the native HVT oligomer, and was not active in immunofluorescence. The monospecific antibody to the MDV-B 230 kDa oligomer neutralized and immunoblotted only the two MDV-1 strains but stained cells infected with MDVs of the three serotypes in immunofluorescence. It is concluded that the cross-protective neutralizing epitopes of HVT are located on heat-labile oligomeric forms of antigen B.

Animals↗

PubMed1994

Herpes simplex virus type 1 (HSV-1) UL56 gene is involved in viral intraperitoneal pathogenicity to immunocompetent mice.

A comparison of the pathogenicity in mice of the recombinant herpes simplex virus type 1 (HSV-1) strain HSV-1-M-LacZ, in which the UL56 gene has been deleted, was made with its parental strain F, following infection in different mouse strains. The polymerase chain reaction (PCR) technique was used to study the migration of virus DNA in the mouse model. Tissues from adult mice infected intraperitoneally (IP) with one of three HSV-1 strains (F, HFEM or HSV-1-LacZ) were examined for the presence of viral DNA. DNA of the pathogenic strain F was detected in the adrenal glands, spinal cord, brain, liver and pancreas. DNA of HSV-1-M-LacZ was detected in the same tissues. However, DNA of the apathogenic strain HFEM was detected transiently (on days 2 and 3 p.i., but not days 1, 5 or 7), only in the adrenal glands and no viral DNA was detected in any of the other tissues. HSV-1 pathogenic strains injected intraperitoneally into newborn mice (7 days old) killed most of the mice. In the surviving mice viral DNA of the three virus strains was found in peritoneal exudate cells (PEC), adrenal glands, spinal cord, liver and spleen. It was found that HSV-1-M-LacZ, which lacks the UL56 gene, resembled in pathogenicity to the newborn mice the pathogenic HSV-1 strains F and KOS. The PCR technique was used to trace viral DNA in tissues of the mice which survived HSV-1 infection at 7 weeks of age. Only HSV-1 (KOS) DNA was detected in the pancreas. The brains of these mice did not contain viral DNA. It is suggested that HSV-1 DNA may reside in surviving HSV-1- infected newborn mice in a "latent" state in nonneural tissues.

Adrenal Glands↗

PubMed1994

Need for cellular and humoral immune responses in bovines to ensure protection from foot-and-mouth disease virus (FMDV)--a point of view.

The published studies on immunization of experimental animals, cattle, and sheep with synthetic peptides containing the antigenic domains in FMDV structural protein VP1 were analyzed. The results obtained with various FMDV synthetic peptides designed to stimulate the humoral immune response in bovines were compared to the current knowledge on MHC class I and class II, and the properties of the peptide binding grooves in each of them. X-ray crystallography of MHC class I proteins provided the three-dimensional structure of the peptide binding groove and led to the isolation and identification of "self" and viral peptides that naturally associate with the peptide binding grooves of both types of MHC and HLA molecules. The available knowledge of the amino acid motifs in MHC and HLA class I-bound viral peptides priming the CD8+ cytotoxic T cell responses must be coupled with the understanding of the three-dimensional structure of BoLA class I. This would aid in the development of an experimental approach to induce bovine anti-FMDV CD8+ cytotoxic cells to complement the humoral immune response to FMDV, which is currently achieved by a killed virus vaccine and, at the experimental level, by a peptide vaccine. Stimulation of both cellular and humoral immune responses against FMDV in cattle may reduce the risk of disease and virus shedding.

Amino Acid Sequence↗

PubMed1994

Analysis of the transcription pattern of HSV-1 UL52 and UL53 genes.

The UL52 and UL53 genes of herpes simplex virus type-1 are both located in the BamHI-L DNA fragment, with an overlap of 14 amino acids. An RNase protection experiment was designed to determine the 5' termini of both the UL52 and UL53 mRNAs. The 5' end of the UL52 mRNA was found to be located 100 bp upstream of its ATG initiation codon. Surprisingly, the 5' terminus of the UL53 gene was found to be downstream of its putative initiation codon. Therefore, it was suggested that the translation of the UL53 open reading frame (ORF) starts at an internal initiation codon that is located 55 codons downstream of the putative one. A hybrid selection experiment was performed in which the UL53-specific mRNA was selected from BSC-1 cells infected with HSV-1 KOS and translated in vitro. The translation product of the UL53 message was found to be 32 kD (shorter than the original 37.5 kD ORF). The size of the protein obtained corresponds with the expected translation product starting at the downstream initiation codon. Analysis of the sequence upstream of this initiation codon reveals the presence of a promotor sequence. Therefore, we suggest that the UL53 protein is 54 amino acids shorter than was previously suggested and is located at coordinates 112,341-113,193.

Animals↗

PubMed1994

Dengue fever virus and Japanese encephalitis virus synthetic peptides, with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions, can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)--a novel approach to the protection of humans.

Flaviviruses were reported to induce CD8+ cytotoxic T cells in infected individuals, indicating that nonapeptides, proteolytic cleavage products of the viral precursor protein, enter the endoplasmic reticulum in infected cells and interact with HLA class I molecules. The assembled HLA class I molecules are transported to the plasma membrane and prime CD8+ T cells. Current knowledge of the interaction of viral peptides with HLA molecules is reviewed. Based on this review, an idea is presented to use synthetic flavivirus peptides with an amino acid motif to fit with the HLA class I peptide binding group of HLA haplotypes prevalent in a given population in an endemic area. These synthetic viral peptides may be introduced into the human skin using a lotion containing the peptides ("Peplotion") together with substances capable of enhancing the penetration of these peptides into the skin to reach Langerhans cells. The peptide-treated Langerhans cells, professional antigen-presenting cells, may bind the synthetic viral peptides by their HLA class I peptide-binding grooves. Antigens carrying Langerhans cells are able to migrate and induce the cellular immune response in the lymph nodes. This approach to the priming of antiviral CD8+ cytotoxic T cells may provide cellular immune protection from flavivirus infection without inducing the humoral immune response, which can lead to the shock syndrome in Dengue fever patients. To be able to develop anti-Dengue virus synthetic peptides for populations with different HLA class I haplotypes, it is necessary to develop computational studies to design HLA class I Dengue virus synthetic peptides with motifs to fit the HLA haplotypes of the population living in an endemic region for Dengue fever. Experiments to study Dengue virus and Japanese encephalitis peptides vaccines and their effectiveness in protection against Dengue fever and Japanese encephalitis are needed. The development of human antiviral vaccines for application of viral peptides in a lotion to human skin ("Peplotion") may be useful and affordable for populations of developing countries.

Amino Acid Sequence↗

PubMed1994

Open reading frames in a 4556 nucleotide sequence within MDV-1 BamHI-D DNA fragment: evidence for splicing of mRNA from a new viral glycoprotein gene.

A DNA segment of the MDV-1 BamHI-D fragment was sequenced, and the open reading frames (ORFs) present in the 4556 nucleotide fragment were analyzed by computer programs. Computer analysis identified 19 putative ORFs in the sequence ranging from a coding capacity of 37 amino acids (aa) (ORF-1a) to 684aa (ORF-1). The special properties of four ORFs (1a, 1, 2, and 3) were investigated. Two adjacent ORFs, ORF-1a and ORF-1, were found by computer analysis to have the properties of two introns encoding a glycoprotein: ORF-1a encodes an aa sequence with the properties of a signal peptide, and ORF-1 encodes a polypeptide with a membrane anchor domain and putative N-glycosylation sites in the aa sequence. ORF-1a and ORF-1 were found to be transcribed in MDV-1-infected cells. Two RNA transcripts were detected: a precursor RNA and its spliced form. Both are transcribed from a promoter located 5' to ORF-1a, and splice donor and acceptor sites are used to splice the mRNA after cleavage of a 71-nucleotide sequence. This finding suggest that ORF-1a and ORF-1 are two introns of a new MDV-1 glycoprotein gene. The DNA sequence containing ORF-1 was transiently expressed in COS-1 cells, and the viral protein produced in these cells was found to react with anti-MDV serotype-1 Antigen B-specific monoclonal antibodies. These studies indicate that the protein encoded by ORF-1 has antigenic properties resembling Antigen B of MDV-1. A gene homologous to ORF-1 was detected in the genome of both MDV-2(SB1) and MDV-3(HVT), which serve as commercial vaccine strains. Two additional ORFs were noted in the 4556 nucleotide sequence: ORF-2, which encodes a 333 aa polypeptide initiating in the UL and terminating in the TRL prior to the putative origin of replication, and ORF-3, which encodes a 155 aa polypeptide that is partly homologous to the phosphoprotein pp38 encoded by the BamHI-H sequence. The 65 N-terminal aa of the two gene products are identical, both being derived from the nucleotide sequences in the TRL and IRL, respectively. Additional homologous aa sequences are the hydrophobic aa domain in the middle of both proteins. The functions of ORF-2, ORF-3, and additional ORFs are under study.

Amino Acid Sequence↗

PubMed1994

HIV-1 proteins in infected cells determine the presentation of viral peptides by HLA class I and class II molecules and the nature of the cellular and humoral antiviral immune responses--a review.

The goals of molecular virology and immunology during the second half of the 20th century have been to provide the conceptual approaches and the tools for the development of safe and efficient virus vaccines for the human population. The success of the vaccination approach to prevent virus epidemics was attributed to the ability of inactivated and live virus vaccines to induce a humoral immune response and to produce antiviral neutralizing antibodies in the vaccinees. The successful development of antiviral vaccines and their application to most of the human population led to a marked decrease in virus epidemics around the globe. Despite this remarkable achievement, the developing epidemics of HIV-caused AIDS (accompanied by activation of latent herpesviruses in AIDS patients), epidemics of Dengue fever, and infections with respiratory syncytial virus may indicate that conventional approaches to the development of virus vaccines that induce antiviral humoral responses may not suffice. This may indicate that virus vaccines that induce a cellular immune response, leading to the destruction of virus-infected cells by CD8+ cytotoxic T cells (CTLs), may be needed. Antiviral CD8+ CTLs are induced by viral peptides presented within the peptide binding grooves of HLA class I molecules present on the surface of infected cells. Studies in the last decade provided an insight into the presentation of viral peptides by HLA class I molecules to CD8+ T cells. These studies are here reviewed, together with a review of the molecular events of virus replication, to obtain an overview of how viral peptides associate with the HLA class I molecules. A similar review is provided on the molecular pathway by which viral proteins, used as subunit vaccines or inactivated virus particles, are taken up by endosomes in the endosome pathway and are processed by proteolytic enzymes into peptides that interact with HLA class II molecules during their transport to the plasma membrane of antigen-presenting cells. Such peptides are identified by T-cell receptors present on the plasma membrane of CD4+ T helper cells. The need to develop viral synthetic peptides that will have the correct amino acid motifs for binding to HLA class I A, B, and C haplotypes is reviewed. The development of HIV vaccines that will stimulate, in an uninfected individual, the humoral (antibody) and cellular (CTL) immune defenses against HIV and HIV-infected cells, respectively, and may lead to protection from primary HIV infection are discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS Vaccines↗

PubMed1994

Nucleotide sequence of the P1 region of serotype Asia1 foot-and-mouth disease virus.

Differences in the amino acid sequence of foot-and-mouth disease virus (FMDV) virion proteins (VP) among the various FMDV serotypes, particularly in the VP1 polypeptide, are the basis for antigenic diversity of this virus group. This phenomenon provides the basis for type diagnosis of FMDV by the polymerase chain reaction (PCR). In order to specifically identify the Asia1 FMDV serotype by PCR, the nucleotide sequence of its P1-coding region was determined. The sequence exhibited over 70% homology with the P1 gene segment of type O1k. The deduced amino acid sequence shares 79% homology with that of the P1 region of serotype O1k.

Amino Acid Sequence↗

PubMed1994

Distribution of Ia antigen positive cells in chicken embryos infected with oncogenic Marek's disease virus (MDV) and MD vaccine viruses of serotypes 1, 2 and 3.

Chick embryos infected at Day 13 of embryonic development (ED) with the oncogenic serotype 1 Marek's Disease Virus, isolate B (MDV-B) and three MDV vaccines (CVI988, SB1 and HVT, serotypes 1, 2 and 3, respectively) and uninfected chick embryos were studied for the distribution of Ia antigen positive dendritic cells (DC), B cells and MDV antigen positive (Ag+) cells in the lymphoid organs and chorioallantoic membrane (CAM). The immunofluorescence study was conducted on acetone-fixed organ touch impressions using monoclonal antibodies to Ia antigen, and MDV serotypes 1, 2 and 3 and polyclonal antibodies to bursal Ig-bearing (Ig+) B cells. DC were found mainly in the thymus and spleen and Ig+ cells in the bursa, thymus and spleen of normal embryos. All virus-infected embryos had MDV Ag+ cells in the spleen. MDV-B and SB1 infected embryos also had MDV Ag+ cells in the bursa, MDV-B Ag+ cells in the CAM and SB1-Ag+ cells in the thymus. Infection with MDV altered the distribution pattern of DC in a serotype-specific manner: to a lesser extent, infection with MDV-B and SB1 induced their appearance in the CAM, while HVT and CVI988 depleted the DC population from all organs except the bursa and the thymus, respectively. Infection with MDV-B depleted the Ig+ cells from all organs. These results suggest that virus-specific patterns of change in the distribution of DC and B cells occur in various tissues and organs of the chick embryo as a result of infection with oncogenic and apathogenic strains of MDV.

Animals↗

PubMed1993

Role of Langerhans cells and other dendritic cells in viral diseases.

Langerhans cells are part of a vast system of potent antigen-presenting cells known under the name of dendritic cells. During the last decade, much has been learned on dendritic cell involvement in the immune response to infectious diseases. This review briefly summarizes our current understanding of the role played by Langerhans cells and other dendritic cells in the pathogenesis of DNA and RNA virus infections. These data may form the basis for the development of innovative approaches in the diagnosis, prevention, and treatment of viral diseases.

Animals↗

PubMed1993

The genome of equine herpesvirus type 2 harbors an interleukin 10 (IL10)-like gene.

A gene was identified within the DNA sequences of the EcoRI DNA fragment N (4.3 kbp) of the genome of equine herpesvirus type 2 (EHV-2) coding for a protein (179 amino acid residues) homologous to the cytokine synthesis inhibitory factor (CSIF; interleukin 10) of the human and mouse, and to the Epstein-Barr virus (EBV) protein BCRF1. This finding is further significant evidence that the interleukin 10 (IL-10) and/or IL-10-like gene can indeed be present in the genomes of members of the herpesviral family.

Amino Acid Sequence↗

PubMed1993

Effect of herpes simplex virus type-1 UL41 gene on the stability of mRNA from the cellular genes: beta-actin, fibronectin, glucose transporter-1, and docking protein, and on virus intraperitoneal pathogenicity to newborn mice.

Infection with HSV-1 is accompanied by the shut-off of cellular gene expression. The virion-associated function is encoded by the viral gene UL41. An HSV-1 mutant, vhs-1, which has a genomic deletion in the UL41 gene, is incapable of inducing the shut-off of cellular gene expression. The effect of HSV-1 infection on the shut-off of the cellular genes (or mRNA degradation) was studied specifically with the cellular genes for beta-actin, fibronectin, glucose transporter-1, and the docking protein. The level of these specific mRNAs was measured in cells infected with several HSV-1 strains and was compared to that of vhs-1- and mock-infected cells. It was possible to demonstrate a marked reduction in the level of the specific mRNA from these cellular genes in cells infected with several HSV-1 strains but not with the vhs-1 mutant. The pathogenicity of the HSV-1 vhs-1 mutant to newborn mice was studied. It was found that the mutant is less pathogenic to newborn mice than its parental strain HSV-1 KOS.

Actins↗

PubMed1993

PCR detection of amplified 132 bp repeats in Marek's disease virus type 1 (MDV-1) DNA can serve as an indicator for critical genomic rearrangement leading to the attenuation of virus virulence.

A radioactive PCR test was developed that amplified the very virulent Marek's disease virus-1 (vvMDV-1) DNA sequence containing the 132 bp repeats. In apathogenic MDV-1 (CVI 988, Rispens), amplified DNA bands containing multiple copies of 132 bp repeats were identified. In the present study this PCR technique was used to monitor the passage level of vvMDV-1 in chicken embryo fibroblasts (CEF) in which the number of tandem 132 bp repeats was increased. It was found that at passage level 32 of vvMDV-1-B isolate, the 132 bp tandem repeat was already markedly amplified and its pattern resembled that of the MDV-1 (CVI 988, Rispens) vaccine virus DNA. In the vvMDV-1Z strain, amplification of the 132 bp repeat was not detectable at a similar passage level. The PCR test demonstrated that the apathogenic MDV-1 Md11/75c virus developed by extensive in vitro passaging has amplified 132 bp DNA repeats similar to those of the commercial vaccine virus (CVI 988, Rispense). It was also found that the pattern of viral RNA from infected cells detectable by Northern blot hybridization was markedly changed from a 2.4 kb RNA species in cells infected with vvMDV-1 viruses, to four RNA species (ranging from 2.2 to 4.4 kb) in cells infected with passage 32 of MDV-1-B strain, to a very large number of undefined RNA species synthesized in cells infected with attenuated MDV-1 viruses (CVI 988, Rispens and Md 11/75c).

Animals↗

PubMed1992

Polymerase chain reaction for differentiation between pathogenic and non-pathogenic serotype 1 Marek's disease viruses (MDV) and vaccine viruses of MDV-serotypes 2 and 3.

A polymerase chain reaction (PCR) test based on primers flanking the 132 bp tandem repeat in pathogenic MDV-1 DNA was developed. These primers amplify a dimer or a trimer 132 bp repeat in pathogenic MDV-1 DNA from blood and organs of commercial chickens with Marek's disease (MD) symptoms. Using the same primers in a radioactive PCR test, it was possible to distinguish between vvMDV-1 and the non-pathogenic MDV-1 CVI-988 vaccine in which the 132 bp repeats in the DNA were increased up to 9 repeats. The MDV-1 specific primers did not amplify MDV-2 (SB1) and MDV-3 (HVT) DNA. Primers prepared according to the nucleotide sequence of MDV-1 antigen A gene amplified MDV-1 DNA only. Specific primers prepared according to the nucleotide sequence of MDV-3 (HVT) antigen A gene amplified MDV-3 DNA but not MDV-1 nor MDV-2 DNA. The results of the present study show that the PCR tests can be used for the early identification of vvMDV-1 DNA in pathological samples from diseased commercial chickens and to distinguish between the vvMDV-1 and the three types of virus vaccines used to immunize chickens. The tests are accurate and can be performed in the presence of vaccine virus DNA in the sample.

Animals↗

PubMed1992

Determination of the coding capacity of the BamHI DNA fragment B of apathogenic Herpes simplex virus type 1 strain HFEM by DNA nucleotide sequence analysis.

Herpes simplex virus type 1 (HSV-1) strain HFEM acquired an apathogenic phenotype due to a deletion within the DNA sequences of the BamHI DNA fragment B of the viral genome. In order to investigate the coding strategy of this particular region of the genome of HSV-1 strain HFEM the DNA nucleotide sequence of the BamHI DNA fragment B was determined. This analysis revealed that the BamHI DNA fragment B of HSV-1 strain HFEM comprises 6593 bp, corresponding to the nucleotide positions (np) 113322 to 117088 and np 120643 to 123465 of the genome of HSV-1 strain 17. According to these data the deletion of the genome of HSV-1 strain HFEM occurred between the np 117089 and 120642. The promoter region of the UL56 gene of HSV-1 strain HFEM is a part of the deleted DNA sequences. Therefore, this gene of HSV-1 strain HFEM is affected and cannot be expressed. The first 35 amino acid (AA) residues of the deduced amino acid sequence of the UL56 open reading frame (ORF) were found to be identical to the amino acid sequence of the UL56 genes of HSV-1 strains 17 and F. However, due to a deletion at np 3494 of the BamHI DNA fragment B of HSV-1 strain HFEM the amino acid composition of the predicted UL56 gene of HSV-1 strain HFEM is different from HSV-1 strain 17 between amino acid positions 36 and 233. In addition the deduced amino acid sequence of the IRL (inverted repeat of the long segment) copy of the IE110 gene of HSV-1 strain HFEM was found to be about 342 amino acids shorter than the amino acid sequence of IE110 gene of HSV-1 strain 17 (775 AA). This was based on a point mutation which was detected within the DNA sequences of Exon 3 of this copy of IE110 gene of HSV-1 strain HFEM.

Amino Acid Sequence↗

PubMed1992

Antigen B of the vaccine strains of Marek's disease virus and herpesvirus of turkeys presents heat-labile group and serotype specific epitopes.

Antigen B of Marek's disease virus (MDV) vaccine strains CVI988 and SB1 (serotypes 1 and 2) and herpesvirus of turkeys (HVT) (serotype 3) is formed of oligomeric molecules that are detergent-stable and heat-labile. Immunoblots of native membranal extracts of HVT- and MDV-infected chick embryo fibroblasts (CEF) probed with avian monoserotypic antisera, murine monoclonal antibodies (mAb) to the three serotypes and mAb to antigen B showed two distinct patterns of high molecular weight oligomeric antigens. Serotypes 1 and 3 vaccine viruses formed one set and serotype 2, the other. Avian monotypic sera to serotypes 1 and 3 viruses detected two high molecular weight bands of 230 and > or = 300 kDa in MDV-1 and HVT-infected CEF but only a weak diffuse zone ranging from 130 to 230 kDa in extracts of SB1-infected CEF. No 300 kDa band was discernible in the SB1 extract when blotted with avian monotypic 1 and 3 antisera. MAbs to MDV serotypes 1 and 3 and to antigen B also detected the 230 and > or = 300 kDa antigens, while the mAb to SB1 detected a 50 kDa antigen in the SB1-infected extract only. Furthermore, the antigen B mAb did not reveal high mol. wt. oligomers in SB1-infected CEF extracts. Antigen B oligomers were rapidly destroyed by heating at 95 degrees C and the rate of denaturation of the 230 and > or = 300 kDa oligomers differed for each of the three vaccine viruses. We propose that antigen B of MDV1 and HVT has a complex conformation created by juxtaposition of dimers (230-250 kDa) and trimers (> or = 300 kDa), and is inserted in the infected cell membrane so that conformational, discontinuous epitopes are formed in addition to continuous epitopes. It appears that HVT protects chickens against oncogenic strains of MDV1 by virtue of the cross reactivity of the conformational determinants located on these oligomers. Serotype 2 vaccine shares some of its antigenic determinants with serotypes 1 and 3, while its unique immunogenic features form the basis of the protective synergism achieved when serotypes 2 and 3 vaccines are combined together.

Animals↗

PubMed1992

Detection of IL-1 beta, TNF-alpha, and IL-6 gene transcription by the polymerase chain reaction in keratinocytes, Langerhans cells and peritoneal exudate cells during infection with herpes simplex virus-1.

Interleukin-1, tumour necrosis factor-alpha and interleukin-6 are considered to be major mediators of inflammatory processes. In the present study, cytokine gene transcription was detected by the polymerase chain reaction technique during cutaneous and intraperitoneal infection with herpes simplex virus-1. Epidermal cell suspensions obtained from mice infected with herpes simplex virus-1 in the ear pinna were enriched or depleted in Langerhans cells by immunomagnetic fractionation. Herpes simplex virus-1 infection in the skin was found to induce interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene transcription in keratinocytes at 24 hours post-infection. Gene transcription declined by 48 hours post-infection. Induction of interleukin-1 beta and tumour necrosis factor-alpha but not of IL-6 gene transcription was detected in Langerhans cells obtained from infected mice at 24 hours post-infection. In order to study cytokine gene transcription during intraperitoneal infection with herpes simplex virus-1, peritoneal exudate cells were obtained from infected mice. Maximal levels of interleukin-1 beta, tumour necrosis factor-alpha, and interleukin-6 mRNA were found in peritoneal exudate cells 6 hours after infection. RNA transcription declined at 24 hours post-infection and was no longer detectable at 48 hours post-infection. Since the higher susceptibility of newborn mice to intraperitoneal herpes simplex virus-1 infection has been suggested to be related to defective cytokine production, cytokine gene transcription was compared in peritoneal exudate cells obtained from infected newborn and adult mice. No significant differences in interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene expression were observed in peritoneal exudate cells obtained from newborn mice as compared with adult mice. In conclusion, cutaneous and intraperitoneal infection with herpes simplex virus-1 induces interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene transcription in epidermal and peritoneal exudate cells.

Animals↗

PubMed1992

Recombinant interleukin-1 alpha, interleukin-2 and M-CSF-1 enhance the survival of newborn C57BL/6 mice inoculated intraperitoneally with a lethal dose of herpes simplex virus-1.

Recombinant Interleukin-1 alpha (IL-1 alpha), Interleukin-2 (IL-2) and recombinant macrophage colony-stimulating factor-1 (M-CSF-1) as well as combinations of IL-2 and M-CSF-1 were studied for their ability to protect seven-day-old C57BL/6 mice against HSV-1 infection. Treatment of the mice with IL-2, M-CSF-1 or combinations of IL-2 and M-CSF-1 significantly increased survival rates. Treatment with IL-1 alpha (10 U and 100 U/mouse) was most effective in protection against HSV-1, resulting in significantly increased survival rates more than four times greater than the survival rate of the infected control group.

Animals↗