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1.
Biology (Basel) ; 12(4)2023 Mar 25.
Article in English | MEDLINE | ID: mdl-37106700

ABSTRACT

Engagement of PRRs in recognition of PAMPs or DAMPs is one of the processes that initiates cellular stress. These sensors are involved in signaling pathways leading to induction of innate immune processes. Signaling initiated by PRRs is associated with the activation of MyD88-dependent signaling pathways and myddosome formation. MyD88 downstream signaling depends upon the context of signaling initiation, the cell (sub)type and the microenvironment of signal initiation. Recognition of PAMPs or DAMPs through PRRs activates the cellular autonomous defence mechanism, which orchestrates the cell responses to resolve specific insults at the single cell level. In general, stressed endoplasmic reticulum is directly linked with the induction of autophagy and initiation of mitochondrial stress. These processes are regulated by the release of Ca2+ from ER stores accepted by mitochondria, which respond through membrane depolarization and the production of reactive oxygen species generating signals leading to inflammasome activation. In parallel, signaling from PRRs initiates the accumulation of misfolded or inappropriately post-translationally modified proteins in the ER and triggers a group of conserved emergency rescue pathways known as unfolded protein response. The cell-autonomous effector mechanisms have evolutionarily ancient roots and were gradually specialized for the defence of specific cell (sub)types. All of these processes are common to the innate immune recognition of microbial pathogens and tumorigenesis as well. PRRs are active in both cases. Downstream are activated signaling pathways initiated by myddosomes, translated by the cellular autonomous defence mechanism, and finalized by inflammasomes.

3.
Travel Med Infect Dis ; 12(1): 84-7, 2014.
Article in English | MEDLINE | ID: mdl-24176669

ABSTRACT

Coinfection by HIV and syphilis has become a growing problem due to the re-appearance of unsafe sexual practices in the era of potent anti-retroviral drugs. We describe a repeated import of syphilis by a couple of men-who-have-sex-with-men from Thailand to Czech Republic likely due to non-adherence of the patients to physician recommendations. Such cases can become foci for dissemination of once locally rare infections and present a danger for the community.


Subject(s)
HIV Infections/microbiology , Homosexuality, Male , Syphilis/virology , Coinfection , Czech Republic , HIV Infections/ethnology , HIV Infections/immunology , Humans , Male , Patient Compliance , Prevalence , Recurrence , Syphilis/ethnology , Syphilis/immunology , Syphilis/transmission , Thailand/ethnology
4.
J Clin Virol ; 50(1): 72-5, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21056000

ABSTRACT

Varicella zoster virus typically causes a benign disease in childhood called varicella (chickenpox) and can reactivate in adults as a dermatomally distributed, painful rash illness known as herpes zoster (HZ). Infection with VZV can however lead to severe complications in immunocompromised patients that can result in hospitalization and, occasionally, death. Here we describe a patient, who acquired primary VZV infection during a 3-week-long treatment regimen with corticosteroids. The disease took a fulminant course, leading to a liver failure and severe coagulopathy. The patient died 9 days following hospital admission, despite intensive antiviral and supportive treatment. Wild-type VZV DNA was detected from multiple samples from esophagus, liver and skin. Genotypic analysis based on single nucleotide polymorphism profiles in open reading frames (ORFs) 21, 22 and 50 identified this strain as a clade 4 isolate, which is typically found in tropical countries. This is the first description of a clade 4 strain from a patient in the Czech Republic.


Subject(s)
Chickenpox/complications , Hepatitis/complications , Herpesvirus 3, Human/physiology , Immunocompromised Host , Adult , Czech Republic , Fatal Outcome , Female , Genes, Viral/genetics , Genotype , Hepatitis/pathology , Herpesvirus 3, Human/classification , Herpesvirus 3, Human/genetics , Humans , Immunosuppressive Agents/adverse effects
5.
Virology ; 383(2): 216-25, 2009 Jan 20.
Article in English | MEDLINE | ID: mdl-19019403

ABSTRACT

Phylogenetic analysis of 19 complete VZV genomic sequences resolves wild-type strains into 5 genotypes (E1, E2, J, M1, and M2). Complete sequences for M3 and M4 strains are unavailable, but targeted analyses of representative strains suggest they are stable, circulating VZV genotypes. Sequence analysis of VZV isolates identified both shared and specific markers for every genotype and validated a unified VZV genotyping strategy. Despite high genotype diversity no evidence for intra-genotypic recombination was observed. Five of seven VZV genotypes were reliably discriminated using only four single nucleotide polymorphisms (SNP) present in ORF22, and the E1 and E2 genotypes were resolved using SNP located in ORF21, ORF22 or ORF50. Sequence analysis of 342 clinical varicella and zoster specimens from 18 European countries identified the following distribution of VZV genotypes: E1, 221 (65%); E2, 87 (25%); M1, 20 (6%); M2, 3 (1%); M4, 11 (3%). No M3 or J strains were observed.


Subject(s)
Chickenpox/virology , Herpes Zoster/virology , Herpesvirus 3, Human/classification , Herpesvirus 3, Human/genetics , Polymorphism, Single Nucleotide , Chickenpox/epidemiology , Europe/epidemiology , Genotype , Herpes Zoster/epidemiology , Herpesvirus 3, Human/isolation & purification , Humans , Molecular Epidemiology , Molecular Sequence Data , Phylogeny , Sequence Analysis, DNA , Sequence Homology
6.
Clin Infect Dis ; 48(1): e6-8, 2009 Jan 01.
Article in English | MEDLINE | ID: mdl-19025497

ABSTRACT

During a suspected monkeypox outbreak in the Republic of Congo, we documented transmission of varicella-zoster virus (VZV) infection with palm and sole manifestations among 5 family members. Genotyping results confirmed the VZV strain European E2, a genotype not previously reported in Africa. VZV with palm and sole involvement should be considered when differentiating a monkeypox diagnosis.


Subject(s)
Hand/pathology , Herpes Zoster/physiopathology , Herpes Zoster/transmission , Leg/pathology , Adolescent , Adult , Child , Congo/epidemiology , DNA, Viral/genetics , Diagnosis, Differential , Family Health , Female , Genotype , Herpes Zoster/diagnosis , Herpes Zoster/epidemiology , Herpesvirus 3, Human/classification , Herpesvirus 3, Human/genetics , Herpesvirus 3, Human/isolation & purification , Humans , Infant , Male , Mpox (monkeypox)/diagnosis , Phylogeny
7.
J Infect Dis ; 198(10): 1444-7, 2008 Nov 15.
Article in English | MEDLINE | ID: mdl-18826373

ABSTRACT

A previously healthy boy who had received varicella vaccine developed herpes zoster with meningitis. The vaccine strain recovered from scabs of 3 skin lesions had the wild-type allele at position 108111, a vaccine marker never previously associated with vaccine-associated adverse events. The vaccine strain from cerebrospinal fluid also contained mutations never previously observed at vaccine-associated single nucleotide polymorphisms that would alter amino acid sequences in ORF54 and ORF59. The presence of distinct strains in skin lesions and cerebrospinal fluid indicate that >1 variant strain may reactivate to cause herpes zoster.


Subject(s)
Chickenpox Vaccine/adverse effects , Genetic Variation , Herpes Zoster/virology , Herpesvirus 3, Human/genetics , Meningitis/virology , Chickenpox/prevention & control , Child , DNA, Viral/analysis , DNA, Viral/cerebrospinal fluid , Genotype , Herpes Zoster/etiology , Herpesvirus 3, Human/isolation & purification , Humans , Male , Sequence Alignment , Skin Diseases, Viral/virology
8.
J Virol ; 81(23): 12758-65, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17898056

ABSTRACT

Whole genome phylogenetic analysis in this study resolved a total of five major genotypes among the 22 varicella-zoster virus (VZV) strains or isolates for which complete genomic sequences are available. Consistent with earlier publications we have designated these genotypes European 1 (E1), European 2 (E2), Japanese (J), mosaic 1 (M1), and mosaic 2 (M2). Single nucleotide polymorphism (SNP) analysis performed in a whole-genome alignment revealed that VZV isolates of all five genotypes can be accurately genotyped using SNPs from two amplicons: open reading frame 22 (ORF22) and either ORF21 or ORF50. This modified approach identifies all of the genotypes observed using any of the published genotyping protocols. Of 165 clinical varicella and zoster isolates from Australia and New Zealand typed using this approach, 67 of 127 eastern Australian isolates were E1, 30 were E2, 16 were J, 10 were M1, and 4 were M2; 25 of 38 New Zealand isolates were E1, 8 were E2, and 5 were M1. VZV strain diversity in eastern Australia is thus broader than has been described for any other region, including Europe, Africa, and North America. J strains were far more prevalent than previously observed in countries other than Japan. Two-amplicon typing was in complete accord with genotypes derived using SNP in multiple ORFs (ORFs 1, 21, 22, 38, 50, 54, and 62). Two additional minor genotypes, M3 and M4, could also be resolved using two-amplicon typing.


Subject(s)
Genetic Techniques , Herpesvirus 3, Human/classification , Herpesvirus 3, Human/genetics , Polymorphism, Single Nucleotide , Australia , DNA, Viral/genetics , Genome, Viral/genetics , Genotype , Herpes Zoster/virology , Herpesvirus 3, Human/isolation & purification , Humans , Molecular Epidemiology , New Zealand , Open Reading Frames , Phylogeny , Sensitivity and Specificity , Sequence Homology
9.
J Virol ; 78(8): 3811-6, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15047796

ABSTRACT

The currently used smallpox vaccine is associated with a high incidence of adverse events, and there is a serious need for a safe and effective alternative vaccine. Here, we carried out a longitudinal evaluation of vaccinia virus-specific CD4 and CD8 T cells in smallpox-vaccinated individuals by using a highly sensitive intracellular cytokine staining assay. Our results demonstrate that, in addition to the CD8 response, the smallpox vaccinations raised a robust CD4 response with a Th1-dominant cytokine profile. These CD4 T cells were stable and exhibited only a twofold contraction between peak effector and memory phases compared with an approximate sevenfold contraction for CD8 cells. A significant proportion of vaccinated individuals lost detectable CD8 memory while maintaining CD4 memory. After a booster immunization, these individuals generated a robust CD8 response, which some of them rapidly lost. Thus, the current smallpox vaccine provides long-lasting CD4 help that may be critical for long-lived B-cell memory. We suggest that the provision of adequate CD4 help for CD8 and humoral effector functions will be critical to the success of the next generation of smallpox vaccines.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Smallpox Vaccine/pharmacology , Variola virus/immunology , Adult , Case-Control Studies , Cohort Studies , Cytokines/biosynthesis , Humans , Immunization, Secondary , Immunologic Memory , Longitudinal Studies , Smallpox Vaccine/administration & dosage , Smallpox Vaccine/immunology , Th1 Cells/immunology , Vaccinia virus/immunology
10.
AIDS Res Hum Retroviruses ; 19(10): 883-90, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14585220

ABSTRACT

Coadministration of pVecB7, a replication-defective SIV DNA vaccine, with interleukin-12 and GM-CSF expression plasmids, induced markedly enhanced control of viral replication and disease-free survival in macaques challenged intrarectally with pathogenic SIVsmE660. Protective mechanisms correlated with broader cell-mediated immune responses to the first two-thirds of the SIV Gag protein and possibly with enhanced SIVsmE660 antibody neutralization at set point, but not with pre- or early postchallenge SIVsmE660 neutralizing antibody production.


Subject(s)
Gene Products, gag/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Interleukin-12/administration & dosage , SAIDS Vaccines/administration & dosage , Simian Acquired Immunodeficiency Syndrome/prevention & control , Animals , Antibodies, Viral/immunology , Drug Administration Schedule , Drug Therapy, Combination , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Interleukin-12/immunology , Macaca mulatta , SAIDS Vaccines/immunology , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Acquired Immunodeficiency Syndrome/virology , Simian Immunodeficiency Virus/immunology , T-Lymphocytes/immunology , Vaccines, DNA/administration & dosage , Vaccines, DNA/immunology
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