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J. Rajcani

Slovak Academy of Sciences, Institute of Virology, Emeritus

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Rajčáni Július, ass. Prof., MD, PhD, ScD, retired virologist and pathologist, borne in Bratislava, 9.2.1937 (Slovakia), graduated at Medical Faculty of Comenius University in Bratislava (1960), PhD at the Institute of Virology, Slovak Academy of Sciences (SAS), Bratislava (1970), ScD at SAS (1985). From 1960 to 1966 fellow at the Department of Pathology, Med. Faculty, Bratislava, specialization in pathology grade I (1963). From 1966 to 1970 research fellow at the Inst. of Virology, SAS, since 1970 scientist, from 1985 senior scientist and Head of the Dept. of Pathogenesis at the Virology Institute of SAS. Ass. Prof. at the Dept. of Microbiology, Jessenius Medical Faculty of Comenius University, Martin (2001-2013, Head of the Dept. of Microbiology), emeritus scientist from 2008. Member of the Presidium of SAS in 1995-1998, executive editor of Acta virologica (1981-1991). Visiting fellow at Dept. of Virology, Hosp. for Sick Children, Toronto, Canada (1970-1971), visiting scientist at Dept. of Patology, University of Cambridge, UK (1978) and at the Cancer Res. Ctr. Heidelberg, Germany (in 1988, 1989 and 1991). Visiting profesor at the Natn. Inst. of Neural Diseases and Stroke, NIH, Bethesda, MD, USA (1992-1993). Research adviser at RTE (Res. Triangle Europe) Company, Mosonmagyaróvár, Hungary (2009-2020), research adviser at Pathology s.r.o., Martin, Slovakia (2008-2018). Author (or coauthor) of 7 books, 20 chapters in books and over 200 genuine research papers (over 100 in English). Recipient of Jessenius Gold Medal (Slov. Acad. Science), Gold Medal of Slovak Medical Society, Manninger Medal of Hungarian Microbiology Society and Patočka Medal (Czech and Slovak Society of Microbiology).

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Papers by J. Rajcani

Herpes Simplex Virus 1 (HSV1) Strain HSZP Glycoprotein B Gene: Comparison of Mutations among Strains Differing in Virulence

Virus Genes, 2000

The nonpathogenic HSZP strain of HSV-1 induces large polykaryocytes due to a syn3 mutation (His f... more The nonpathogenic HSZP strain of HSV-1 induces large polykaryocytes due to a syn3 mutation (His for Arg at residue 858) in the C-terminal endodomain of glycoprotein B (gB) (40). We determined the nucleotide (nt) sequence of the UL27 gene specifying the gB polypeptide of HSZP (gBHSZP) and found 3 mutations in its ectodomain at aminoacids (aa) 59, 79 and 108.

Attenuated cortisol reactivity to psychosocial stress is associated with greater visual dependency in postural control

Psychoneuroendocrinology, 2019

Characterization of glycoprotein C of HSZP strain of herpes simplex virus 1

Acta virologica, 2000

Sequences of UL44 genes of strains HSZP, KOS and 17 of herpes simplex virus 1 (HSV-1) were determ... more Sequences of UL44 genes of strains HSZP, KOS and 17 of herpes simplex virus 1 (HSV-1) were determined and the amino acid sequences of corresponding glycoproteins (gC) were deduced. In comparison with the 17 strain, the HSZP strain showed specific changes in 3 nucleotides and in 2 amino acids (aa 139 and 147, both from Arg to Trp) in the antigenic locus LII. The change at aa 147 was situated within the GAG-binding epitope. In a similar comparison, KOS strain had changes in 3 nucleotides and 3 amino acids (aa 3, 14, and 300). The UL44 genes of HSZP and KOS strains were expressed in insect Sf-21 cells by means of the baculovirus (Bac-to-Bac) expression system. As shown by immunoblot analysis, both the recombinant baculoviruses (B1-HSZP and B6-KOS) expressed a glycosylated gC, the M(r) of which (116 K) was lower than that of gC synthesized in Vero cells (129 K) infected with strains HSZP or KOS. In addition, smaller gC-specific proteins (of apparent M(r) of 50-58 K and 98 K) correspondi...

Expression of herpes simplex virus 1 glycoprotein B by a recombinant vaccinia virus and protection of mice against lethal herpes simplex virus 1 infection

Proceedings of the National Academy of Sciences, 1987

The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modifi... more The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modified at the 5' end by in vitro oligonucleotide-directed mutagenesis. The modified gB gene was inserted into the vaccinia virus genome and expressed under the control of a vaccinia virus promoter. The mature gB glycoprotein produced by the vaccinia virus recombinant was glycosylated, was expressed at the cell surface, and was indistinguishable from authentic HSV-1 gB in terms of electrophoretic mobility. Mice immunized intradermally with the recombinant vaccinia virus produced gB-specific neutralizing antibodies and were resistant to a lethal HSV-1 challenge.

Cumulative cortisol concentrations in hair of patients with atopy are lower than in healthy subjects and are not related to their perceived stress experience

Stress, 2020

Abstract Patients with atopy were found to exhibit blunted cortisol responses to acute stress sti... more Abstract Patients with atopy were found to exhibit blunted cortisol responses to acute stress stimuli. The aim of this study was to test the hypothesis that cumulative cortisol concentrations in the hair of patients with atopy are lower than in healthy subjects when related to their perceived stress experience. The sample consisted of 31 participants. The most proximal 3 cm of hair (as close to the scalp as possible), reflecting the cumulative cortisol secretion during the previous 3 months, was used for the analysis. Only in 20 subjects (9 patients with atopy and 11 healthy controls), there was a sufficient amount of hair for precise analysis using a new methodology. The results showed lower hair cortisol concentrations in patients with atopy compared to those in controls. The perceived stress scores in patients with atopy and healthy controls were not statistically different. The cortisol concentration/perceived stress score ratios were lower in patients with atopy compared to those in controls. No statistically significant correlation between hair cortisol and long-term experienced stress assessed via perceived stress scale was observed. In conclusion, the cumulative cortisol secretion in the hair of atopic patients is lower than would be expected according to their subjective scores of perceived stress. Most importantly, the previously lower stress hormone increase found in acute stress situations and in children now was confirmed in adult patients with chronic stress load.

Good, Truth and Being: The Ethical Thought of Romano Guardini

Studies in Christian Ethics, 2016

In this article, I present one view of Guardini’s ethics, to which he dedicated his late academic... more In this article, I present one view of Guardini’s ethics, to which he dedicated his late academic life. Christian ethics for Guardini is only a natural consequence of the whole Christian existence and thus unique. Therefore, it is fundamentally a christocentric ethics but it affirms also the being of man as creature and hence realistic. It is indeed based on the nature of man, but not natural in the biological sense. I focus on the interpretation of the good that is never in Guardini’s eyes a mere concept, but objectively existing and concrete. I point out that ethics is always connected with the personal dimension, that man’s doing is radically a working-with-God, and that in and through action man grasps and perfects himself. Christian ethics is a participation in Christ’s properties and conformity to him, who is the personal and living norm of the new life.

Experimental infection of monkeys with Kemerovo virus

Acta virologica, 1970

Abstract 50. Possible role of viruses affecting the CNS in the etiology of psychoses and chronic mental disorders

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1985

Detection of Interleukin 6 (IL-6) antigen in the head and neck carcinoma cells

Clinical and Medical Investigations, 2019

Background: Interleukin 6 (IL-6) is a pleiotropic cytokine produced not only by inflammatory cell... more Background: Interleukin 6 (IL-6) is a pleiotropic cytokine produced not only by inflammatory cells, but also by the squamous epithelium of oral cavity, tongue and/ or laryngeal mucosa (probably explaining its presence in saliva and respiratory secretions). Methods: Immunohistochemical staining for IL-6 antigen was performed in histological sections coming from 98 head and neck squamous cell carcinoma (HNSCC) samples using monospecific IL-6 antibody (rabbit anti-IL-6 serum purchased from Abcam, product Ab6672) and taking advantage of the BenchMark Ultra IHC/ ISH staining module (Ventana Discovery XT automated system, Tuscon, USA). Results: The expression of IL-6 antigen was examined in a total of the 98 head and neck squamous cell carcinoma (HNSCC) samples, i.e. 33 laryngeal, 55 tongue and 10 nasal cavity specimens, along with 18 relevant normal tissue samples (negative controls) and, in addition, in 10 non-HNSCC tumours (alternative tumour controls). Immuhistochemical staining confirmed the presence of IL-6 antigen in the cytoplasm of carcinoma cells as well as in the stroma of all the HNSCC tumours (100%). In conventional squamous carcinomas a rather confluent staining of IL-6 could be seen in the cytoplasm of dysplastic prickle cells, while in anaplastic cells of undifferentiated carcinomas a less intensive fine granular staining pattern dominated. For comparison, occasional and less intensive staining for the IL-6 antigen was seen in 5 out of 10 alternative carcinomas (50%) and/or in 10 out of 16 (60%) relevant normal tissue controls. Conclusion: We confirmed the widespread expression IL-6 antigen as detected by immunohistochemical staining in all the HNSCC samples examined (100% positive), regardless whether using purchased slides or sections prepared from our domestic biopsy material. A proportion (60 %) of the normal laryngeal and mouth cavity epithelium was positive as well, though in the letter, the frequency and intensity of antigen expression was considerably lower.

Detection of interleukin 6 (IL-6) antigen in the head and neck carcinoma cells

Background: Interleukin 6 (IL-6) is a pleiotropic cytokine produced not only by inflammatory cell... more Background: Interleukin 6 (IL-6) is a pleiotropic cytokine produced not only by inflammatory cells, but also by the squamous epithelium of oral cavity, tongue and/or laryngeal mucosa explaining its presence in saliva and some respiratory secretions. Methods: Immunohistochemical staining for IL-6 antigen was performed in histological sections coming from 106 head and neck squamous cell carcinoma (HNSCC) samples using monospecific IL-6 antibody (rabbit anti-IL-6 serum purchased from Abcam, product Ab6672) and taking advantage of the BenchMark Ultra IHC/ISH staining module (Ventana Discovery XT automated system, Tuscon, USA). Results: The expression of IL-6 antigen was examined in 35 laryngeal, 61 tongue and 10 nasal cavity squamous cell carcinomas (SCC) along with 16 relevant normal tissue samples (negative tumour controls) and 10 non-HNSCC tumours (alternative tumour controls). Immuhistochemical staining has confirmed the abundant presence of given antigen in the cytoplasm as well as in the stroma of all the HNSCC tumours (100%), in contrast to low intensity staining of the sections from 10 out of 16 negative tumour controls (63% positive) and/or of 5 alternative carcinomas (50% positive). Abundant extracellular deposits of the IL-6 antigen could be found in the stroma of all the HNSCC tumours. In the differentiated (grade I) HNSCC samples, rather confluent staining of the IL-6 could be seen the cytoplasm of dysplastic prickle cells, while in anaplastic cells of 2 undifferentiated (grade II and/or grade III) carcinomas the less extensive fine granular staining pattern dominated. Conclusion: We confirmed the widespread expression IL-6 antigen as detected by immunohistochemical staining in all the HNSCC samples (100% positive), regardless whether in purchased slides or those prepared from domestic biopsy material. A proportion (63 %) of the normal laryngeal and mouth cavity tissues was positive as well, though the degree and intensity of given antigen expression was considerably lower.

Virus Research Achievements 2

Glycoprotein K Specified by Herpes Simplex Virus Type 1 Is Expressed on Virions as a Golgi Complex-Dependent Glycosylated Species and Functions in Virion Entry

To facilitate detection of glycoprotein K (gK) specified by herpes simplex virus, a 12-amino-acid... more To facilitate detection of glycoprotein K (gK) specified by herpes simplex virus, a 12-amino-acid epitope tag was inserted within gK domain III. Recombinant virus gKprotC-DIII, expressing the tagged gK, was isolated. This virus formed wild-type plaques and replicated as efficiently as the wild-type KOS virus in Vero cells. Anti-protein C MAb detected high-mannose and Golgi complex-dependent glycosylated gK within cells as well as on purified virions. The gK-null virus ⌬gK (gK ؊/؊) entered Vero cells substantially more slowly than the wild-type KOS (gK ؉/؉), while ⌬gK virus grown in complementing VK302 cells (gK ؊/؉) entered with entry kinetics similar to those of the KOS virus.

Oncogenesis and Herpesviruses II. Part 1: Biochemistry of Viral Replication and in Vitro Transformation. G. de-Thé , M. A. Epstein , H. zur HausenOncogenesis and Herpesviruses II. Part 2: Epidemiology, Host Response and Control. G. de-The , M. A. Epstein , H. zur Hausen

The Quarterly Review of Biology, 1977

Experimental efficacy of an herpes simplex virus type 1 subunit vaccine: uncertain immunomodulation by a potent antigen

Glycoprotein K of Herpes Simplex Virus: A Transmembrane Protein Encoded by the UL53 Gene which Regulates Membrane Fusion

Herpes Simplex Virus Type 1 (HSV1) Strain HSZP Host Shutoff Gene: Nucleotide Sequence and Comparison with HSV1 Strains Differing in Early Shutoff of Host Protein Synthesis

Virus Genes, 1997

The UL41 gene of the HSZP strain of herpes simplex virus type 1 (HSV-1) defective with respect to... more The UL41 gene of the HSZP strain of herpes simplex virus type 1 (HSV-1) defective with respect to the early shutoff of host protein synthesis was sequenced and compared with the corresponding HSV-1 strain KOS and 17 gene sequences. In comparison with strain 17, nine mutations (base changes) were HSZP specific, five KOS specific and four were common for both

The syn3 strain HSZP of herpes simplex virus type 1 (HSV1) is not pathogenic for mice and shows limited neural spread

Virus Research, 1996

Strain HSZP of the herpes simplex virus type 1 (HSV-1) forms large giant cells in vitro. This pro... more Strain HSZP of the herpes simplex virus type 1 (HSV-1) forms large giant cells in vitro. This property was lbund associated with a mutation that alters the codon CGC (in the strain KOS or 17 sequence) to CAC (in the HSZP sequence), changing the amino acid 857 from arginine to histidine in the cytoplasmic domain of the glycoprotein B (gB) polypeptide chain. Giant cell formation by ANGpath was attributed to a mutation that alters the codon GCC (in KOS and strain 17 sequences) to GTC (in ANGpath sequence) changing the amino acid 854 in the same (syn 3) region of the gB molecule. In contrast to the ANGpath virus, which is pathogenic (1 LDs0 < 1 × l0 4 PFU) for adult DBA/2 mice after peripheral inoculation, strain HSZP was never found to be lethal for adult mice. Whereas ANGpath-infected mice which survived acute infection frequently (79%) developed latency in the regional sensory ganglion (as proved by virus reactivation during explantation), latent HSZP reactivated in ganglion culture at a considerably reduced rate (21%). Only 10-day-old DBA/2 mice were sensitive to HSZP infection. In these, HSZP spread from the site of peripheral administration mainly by hematogenous route. The neural spread of HSZP in suckling DBA/2 mice was manifested by the involvement of vegetative neurons in the wall of the small intestine and in the retroperitoneal vegetative ganglia. We conclude that HSZP, a polykaryocyte-forming strain with a mutation in the syn 3 region II, shows limited neuroinvasity for mice after peripheral administration.

Interference of the low-pH inactivated herpes simplex virus type 1 (HSV-1) strain HSZP with the early shutoff function of superinfecting HSV-1 strain KOS

Virus Research, 1999

In former studies, we described that the HSZP strain of herpes simplex virus type 1 (HSV-1) was d... more In former studies, we described that the HSZP strain of herpes simplex virus type 1 (HSV-1) was defective with respect to the early shutoff of host protein synthesis but was effective at interfering with the early shutoff function of the HSV-1 strain KOS, even when heat-inactivated or neutralized by antibody. However, the HSZP strain failed to interfere when inactivated with zinc ions or purified from cells treated with 2-deoxy-D-glucose. In this study, we provide evidence that the ability of the purified low-pH inactivated (citrate buffer, pH 3.0) and gel-filtered (Sephadex G-25) HSZP virions to adsorb host cells was not significantly affected. However, their ability to induce interference with the early shutoff function of the superinfecting HSV-1 strain KOS was restricted. In comparison with native virus, up to eight times more low-pH inactivated HSZP virions were needed to interfere with the shutoff by strain KOS. The interference was not due to exclusion of strain KOS by HSZP at the level of adsorption and/or penetration. The restriction was partially overcome by treatment of the cells with polyethylene glycol after adsorption of the low-pH inactivated HSZP virions. This observation indicates that the direct fusion of the virion envelope of low-pH inactivated HSZP with the plasma cell membrane was predominantly hampered.

Susceptibility of mouse mammary glands to murine gammaherpesvirus 72 (MHV-72) infection: evidence of MHV-72 transmission via breast milk

Microbial Pathogenesis, 2001

Murine gammaherpesvirus 72 (MHV-72) is a virus of wild rodents and serves as a convenient small a... more Murine gammaherpesvirus 72 (MHV-72) is a virus of wild rodents and serves as a convenient small animal model to understand the pathogenesis of Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV8) infection. In laboratory mice MHV-72 causes an acute infection of lung epithelial cells and establishes the latency in B lymphocytes. In this study, we investigated athymic nude and immunocompetent mice for distribution of virus in organs after infection with MHV-72. Ten days following subcutaneous dorsal injection of nude mice, virus replicated in lungs, lymphoid organs, salivary glands and also in mammary glands. The virus titre decreased by day 21 post-infection in former tissues, but increased in mammary glands. Presence of virus DNA sequences was detected in the lymphoid and non-lymphoid tissues until the death of the animals (about 1 month post-infection). Infection of immunocompetent mice with MHV-72 induced replication of virus up to 42 days post-infection in mammary glands reaching the highest level of infectious virus at day 8 post-infection. These data show that there is latent infection in mice never detected before. Moreover, virus DNA was detected using nested PCR (by amplification of a portion of gp150 gene sequence) in the mammary glands and the milk of mouse mothers infected with MHV-72 2 days before delivery. We demonstrated the presence of virus DNA also in the milk removed from the stomach of non-infected newborn mice, which were nourished by infected mothers (wet-nurses) for 1 or 2 days. The failure to detect the virus DNA in newborn mice lungs confirmed that they did not become infected from wet-nurses by the intranasal route. This suggests that MHV may be naturally transmitted to newborn mice via breast milk.

Transcription at Early Stages of Herpes Simplex Virus 1 Infection and during Reactivation

Intervirology, 2003

Herpes Simplex Virus 1 (HSV1) Strain HSZP Glycoprotein B Gene: Comparison of Mutations among Strains Differing in Virulence

Virus Genes, 2000

The nonpathogenic HSZP strain of HSV-1 induces large polykaryocytes due to a syn3 mutation (His f... more The nonpathogenic HSZP strain of HSV-1 induces large polykaryocytes due to a syn3 mutation (His for Arg at residue 858) in the C-terminal endodomain of glycoprotein B (gB) (40). We determined the nucleotide (nt) sequence of the UL27 gene specifying the gB polypeptide of HSZP (gBHSZP) and found 3 mutations in its ectodomain at aminoacids (aa) 59, 79 and 108.

Attenuated cortisol reactivity to psychosocial stress is associated with greater visual dependency in postural control

Psychoneuroendocrinology, 2019

Characterization of glycoprotein C of HSZP strain of herpes simplex virus 1

Acta virologica, 2000

Sequences of UL44 genes of strains HSZP, KOS and 17 of herpes simplex virus 1 (HSV-1) were determ... more Sequences of UL44 genes of strains HSZP, KOS and 17 of herpes simplex virus 1 (HSV-1) were determined and the amino acid sequences of corresponding glycoproteins (gC) were deduced. In comparison with the 17 strain, the HSZP strain showed specific changes in 3 nucleotides and in 2 amino acids (aa 139 and 147, both from Arg to Trp) in the antigenic locus LII. The change at aa 147 was situated within the GAG-binding epitope. In a similar comparison, KOS strain had changes in 3 nucleotides and 3 amino acids (aa 3, 14, and 300). The UL44 genes of HSZP and KOS strains were expressed in insect Sf-21 cells by means of the baculovirus (Bac-to-Bac) expression system. As shown by immunoblot analysis, both the recombinant baculoviruses (B1-HSZP and B6-KOS) expressed a glycosylated gC, the M(r) of which (116 K) was lower than that of gC synthesized in Vero cells (129 K) infected with strains HSZP or KOS. In addition, smaller gC-specific proteins (of apparent M(r) of 50-58 K and 98 K) correspondi...

Expression of herpes simplex virus 1 glycoprotein B by a recombinant vaccinia virus and protection of mice against lethal herpes simplex virus 1 infection

Proceedings of the National Academy of Sciences, 1987

The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modifi... more The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modified at the 5' end by in vitro oligonucleotide-directed mutagenesis. The modified gB gene was inserted into the vaccinia virus genome and expressed under the control of a vaccinia virus promoter. The mature gB glycoprotein produced by the vaccinia virus recombinant was glycosylated, was expressed at the cell surface, and was indistinguishable from authentic HSV-1 gB in terms of electrophoretic mobility. Mice immunized intradermally with the recombinant vaccinia virus produced gB-specific neutralizing antibodies and were resistant to a lethal HSV-1 challenge.

Cumulative cortisol concentrations in hair of patients with atopy are lower than in healthy subjects and are not related to their perceived stress experience

Stress, 2020

Abstract Patients with atopy were found to exhibit blunted cortisol responses to acute stress sti... more Abstract Patients with atopy were found to exhibit blunted cortisol responses to acute stress stimuli. The aim of this study was to test the hypothesis that cumulative cortisol concentrations in the hair of patients with atopy are lower than in healthy subjects when related to their perceived stress experience. The sample consisted of 31 participants. The most proximal 3 cm of hair (as close to the scalp as possible), reflecting the cumulative cortisol secretion during the previous 3 months, was used for the analysis. Only in 20 subjects (9 patients with atopy and 11 healthy controls), there was a sufficient amount of hair for precise analysis using a new methodology. The results showed lower hair cortisol concentrations in patients with atopy compared to those in controls. The perceived stress scores in patients with atopy and healthy controls were not statistically different. The cortisol concentration/perceived stress score ratios were lower in patients with atopy compared to those in controls. No statistically significant correlation between hair cortisol and long-term experienced stress assessed via perceived stress scale was observed. In conclusion, the cumulative cortisol secretion in the hair of atopic patients is lower than would be expected according to their subjective scores of perceived stress. Most importantly, the previously lower stress hormone increase found in acute stress situations and in children now was confirmed in adult patients with chronic stress load.

Good, Truth and Being: The Ethical Thought of Romano Guardini

Studies in Christian Ethics, 2016

In this article, I present one view of Guardini’s ethics, to which he dedicated his late academic... more In this article, I present one view of Guardini’s ethics, to which he dedicated his late academic life. Christian ethics for Guardini is only a natural consequence of the whole Christian existence and thus unique. Therefore, it is fundamentally a christocentric ethics but it affirms also the being of man as creature and hence realistic. It is indeed based on the nature of man, but not natural in the biological sense. I focus on the interpretation of the good that is never in Guardini’s eyes a mere concept, but objectively existing and concrete. I point out that ethics is always connected with the personal dimension, that man’s doing is radically a working-with-God, and that in and through action man grasps and perfects himself. Christian ethics is a participation in Christ’s properties and conformity to him, who is the personal and living norm of the new life.

Experimental infection of monkeys with Kemerovo virus

Acta virologica, 1970

Abstract 50. Possible role of viruses affecting the CNS in the etiology of psychoses and chronic mental disorders

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1985

Detection of Interleukin 6 (IL-6) antigen in the head and neck carcinoma cells

Clinical and Medical Investigations, 2019

Background: Interleukin 6 (IL-6) is a pleiotropic cytokine produced not only by inflammatory cell... more Background: Interleukin 6 (IL-6) is a pleiotropic cytokine produced not only by inflammatory cells, but also by the squamous epithelium of oral cavity, tongue and/ or laryngeal mucosa (probably explaining its presence in saliva and respiratory secretions). Methods: Immunohistochemical staining for IL-6 antigen was performed in histological sections coming from 98 head and neck squamous cell carcinoma (HNSCC) samples using monospecific IL-6 antibody (rabbit anti-IL-6 serum purchased from Abcam, product Ab6672) and taking advantage of the BenchMark Ultra IHC/ ISH staining module (Ventana Discovery XT automated system, Tuscon, USA). Results: The expression of IL-6 antigen was examined in a total of the 98 head and neck squamous cell carcinoma (HNSCC) samples, i.e. 33 laryngeal, 55 tongue and 10 nasal cavity specimens, along with 18 relevant normal tissue samples (negative controls) and, in addition, in 10 non-HNSCC tumours (alternative tumour controls). Immuhistochemical staining confirmed the presence of IL-6 antigen in the cytoplasm of carcinoma cells as well as in the stroma of all the HNSCC tumours (100%). In conventional squamous carcinomas a rather confluent staining of IL-6 could be seen in the cytoplasm of dysplastic prickle cells, while in anaplastic cells of undifferentiated carcinomas a less intensive fine granular staining pattern dominated. For comparison, occasional and less intensive staining for the IL-6 antigen was seen in 5 out of 10 alternative carcinomas (50%) and/or in 10 out of 16 (60%) relevant normal tissue controls. Conclusion: We confirmed the widespread expression IL-6 antigen as detected by immunohistochemical staining in all the HNSCC samples examined (100% positive), regardless whether using purchased slides or sections prepared from our domestic biopsy material. A proportion (60 %) of the normal laryngeal and mouth cavity epithelium was positive as well, though in the letter, the frequency and intensity of antigen expression was considerably lower.

Detection of interleukin 6 (IL-6) antigen in the head and neck carcinoma cells

Background: Interleukin 6 (IL-6) is a pleiotropic cytokine produced not only by inflammatory cell... more Background: Interleukin 6 (IL-6) is a pleiotropic cytokine produced not only by inflammatory cells, but also by the squamous epithelium of oral cavity, tongue and/or laryngeal mucosa explaining its presence in saliva and some respiratory secretions. Methods: Immunohistochemical staining for IL-6 antigen was performed in histological sections coming from 106 head and neck squamous cell carcinoma (HNSCC) samples using monospecific IL-6 antibody (rabbit anti-IL-6 serum purchased from Abcam, product Ab6672) and taking advantage of the BenchMark Ultra IHC/ISH staining module (Ventana Discovery XT automated system, Tuscon, USA). Results: The expression of IL-6 antigen was examined in 35 laryngeal, 61 tongue and 10 nasal cavity squamous cell carcinomas (SCC) along with 16 relevant normal tissue samples (negative tumour controls) and 10 non-HNSCC tumours (alternative tumour controls). Immuhistochemical staining has confirmed the abundant presence of given antigen in the cytoplasm as well as in the stroma of all the HNSCC tumours (100%), in contrast to low intensity staining of the sections from 10 out of 16 negative tumour controls (63% positive) and/or of 5 alternative carcinomas (50% positive). Abundant extracellular deposits of the IL-6 antigen could be found in the stroma of all the HNSCC tumours. In the differentiated (grade I) HNSCC samples, rather confluent staining of the IL-6 could be seen the cytoplasm of dysplastic prickle cells, while in anaplastic cells of 2 undifferentiated (grade II and/or grade III) carcinomas the less extensive fine granular staining pattern dominated. Conclusion: We confirmed the widespread expression IL-6 antigen as detected by immunohistochemical staining in all the HNSCC samples (100% positive), regardless whether in purchased slides or those prepared from domestic biopsy material. A proportion (63 %) of the normal laryngeal and mouth cavity tissues was positive as well, though the degree and intensity of given antigen expression was considerably lower.

Virus Research Achievements 2

Glycoprotein K Specified by Herpes Simplex Virus Type 1 Is Expressed on Virions as a Golgi Complex-Dependent Glycosylated Species and Functions in Virion Entry

To facilitate detection of glycoprotein K (gK) specified by herpes simplex virus, a 12-amino-acid... more To facilitate detection of glycoprotein K (gK) specified by herpes simplex virus, a 12-amino-acid epitope tag was inserted within gK domain III. Recombinant virus gKprotC-DIII, expressing the tagged gK, was isolated. This virus formed wild-type plaques and replicated as efficiently as the wild-type KOS virus in Vero cells. Anti-protein C MAb detected high-mannose and Golgi complex-dependent glycosylated gK within cells as well as on purified virions. The gK-null virus ⌬gK (gK ؊/؊) entered Vero cells substantially more slowly than the wild-type KOS (gK ؉/؉), while ⌬gK virus grown in complementing VK302 cells (gK ؊/؉) entered with entry kinetics similar to those of the KOS virus.

Oncogenesis and Herpesviruses II. Part 1: Biochemistry of Viral Replication and in Vitro Transformation. G. de-Thé , M. A. Epstein , H. zur HausenOncogenesis and Herpesviruses II. Part 2: Epidemiology, Host Response and Control. G. de-The , M. A. Epstein , H. zur Hausen

The Quarterly Review of Biology, 1977

Experimental efficacy of an herpes simplex virus type 1 subunit vaccine: uncertain immunomodulation by a potent antigen

Glycoprotein K of Herpes Simplex Virus: A Transmembrane Protein Encoded by the UL53 Gene which Regulates Membrane Fusion

Herpes Simplex Virus Type 1 (HSV1) Strain HSZP Host Shutoff Gene: Nucleotide Sequence and Comparison with HSV1 Strains Differing in Early Shutoff of Host Protein Synthesis

Virus Genes, 1997

The UL41 gene of the HSZP strain of herpes simplex virus type 1 (HSV-1) defective with respect to... more The UL41 gene of the HSZP strain of herpes simplex virus type 1 (HSV-1) defective with respect to the early shutoff of host protein synthesis was sequenced and compared with the corresponding HSV-1 strain KOS and 17 gene sequences. In comparison with strain 17, nine mutations (base changes) were HSZP specific, five KOS specific and four were common for both

The syn3 strain HSZP of herpes simplex virus type 1 (HSV1) is not pathogenic for mice and shows limited neural spread

Virus Research, 1996

Strain HSZP of the herpes simplex virus type 1 (HSV-1) forms large giant cells in vitro. This pro... more Strain HSZP of the herpes simplex virus type 1 (HSV-1) forms large giant cells in vitro. This property was lbund associated with a mutation that alters the codon CGC (in the strain KOS or 17 sequence) to CAC (in the HSZP sequence), changing the amino acid 857 from arginine to histidine in the cytoplasmic domain of the glycoprotein B (gB) polypeptide chain. Giant cell formation by ANGpath was attributed to a mutation that alters the codon GCC (in KOS and strain 17 sequences) to GTC (in ANGpath sequence) changing the amino acid 854 in the same (syn 3) region of the gB molecule. In contrast to the ANGpath virus, which is pathogenic (1 LDs0 < 1 × l0 4 PFU) for adult DBA/2 mice after peripheral inoculation, strain HSZP was never found to be lethal for adult mice. Whereas ANGpath-infected mice which survived acute infection frequently (79%) developed latency in the regional sensory ganglion (as proved by virus reactivation during explantation), latent HSZP reactivated in ganglion culture at a considerably reduced rate (21%). Only 10-day-old DBA/2 mice were sensitive to HSZP infection. In these, HSZP spread from the site of peripheral administration mainly by hematogenous route. The neural spread of HSZP in suckling DBA/2 mice was manifested by the involvement of vegetative neurons in the wall of the small intestine and in the retroperitoneal vegetative ganglia. We conclude that HSZP, a polykaryocyte-forming strain with a mutation in the syn 3 region II, shows limited neuroinvasity for mice after peripheral administration.

Interference of the low-pH inactivated herpes simplex virus type 1 (HSV-1) strain HSZP with the early shutoff function of superinfecting HSV-1 strain KOS

Virus Research, 1999

In former studies, we described that the HSZP strain of herpes simplex virus type 1 (HSV-1) was d... more In former studies, we described that the HSZP strain of herpes simplex virus type 1 (HSV-1) was defective with respect to the early shutoff of host protein synthesis but was effective at interfering with the early shutoff function of the HSV-1 strain KOS, even when heat-inactivated or neutralized by antibody. However, the HSZP strain failed to interfere when inactivated with zinc ions or purified from cells treated with 2-deoxy-D-glucose. In this study, we provide evidence that the ability of the purified low-pH inactivated (citrate buffer, pH 3.0) and gel-filtered (Sephadex G-25) HSZP virions to adsorb host cells was not significantly affected. However, their ability to induce interference with the early shutoff function of the superinfecting HSV-1 strain KOS was restricted. In comparison with native virus, up to eight times more low-pH inactivated HSZP virions were needed to interfere with the shutoff by strain KOS. The interference was not due to exclusion of strain KOS by HSZP at the level of adsorption and/or penetration. The restriction was partially overcome by treatment of the cells with polyethylene glycol after adsorption of the low-pH inactivated HSZP virions. This observation indicates that the direct fusion of the virion envelope of low-pH inactivated HSZP with the plasma cell membrane was predominantly hampered.

Susceptibility of mouse mammary glands to murine gammaherpesvirus 72 (MHV-72) infection: evidence of MHV-72 transmission via breast milk

Microbial Pathogenesis, 2001

Murine gammaherpesvirus 72 (MHV-72) is a virus of wild rodents and serves as a convenient small a... more Murine gammaherpesvirus 72 (MHV-72) is a virus of wild rodents and serves as a convenient small animal model to understand the pathogenesis of Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV8) infection. In laboratory mice MHV-72 causes an acute infection of lung epithelial cells and establishes the latency in B lymphocytes. In this study, we investigated athymic nude and immunocompetent mice for distribution of virus in organs after infection with MHV-72. Ten days following subcutaneous dorsal injection of nude mice, virus replicated in lungs, lymphoid organs, salivary glands and also in mammary glands. The virus titre decreased by day 21 post-infection in former tissues, but increased in mammary glands. Presence of virus DNA sequences was detected in the lymphoid and non-lymphoid tissues until the death of the animals (about 1 month post-infection). Infection of immunocompetent mice with MHV-72 induced replication of virus up to 42 days post-infection in mammary glands reaching the highest level of infectious virus at day 8 post-infection. These data show that there is latent infection in mice never detected before. Moreover, virus DNA was detected using nested PCR (by amplification of a portion of gp150 gene sequence) in the mammary glands and the milk of mouse mothers infected with MHV-72 2 days before delivery. We demonstrated the presence of virus DNA also in the milk removed from the stomach of non-infected newborn mice, which were nourished by infected mothers (wet-nurses) for 1 or 2 days. The failure to detect the virus DNA in newborn mice lungs confirmed that they did not become infected from wet-nurses by the intranasal route. This suggests that MHV may be naturally transmitted to newborn mice via breast milk.

Transcription at Early Stages of Herpes Simplex Virus 1 Infection and during Reactivation

Intervirology, 2003