RESUMO
1. Microglial cell activation occurs during brain injury, ischemia, and in several neurologic disorders. Recently, we isolated a transmissible cytotoxic activity (TCA) from the cerebrospinal fluid of a patient with brain ischemia. Such a TCA, associated with one or more protein(s) that supposedly had undergone in vivo misfolding, causes apoptosis in vitro in different cell lines, including microglial cells. The TCA producing cells and the potential in vivo role of such cytotoxic activity remains to be elucidated. Here, we investigated the in vitro effects of TCA on microglial cell immune functions.2. The murine microglial cell line RR4 was exposed to TCA, and then its response was evaluated as: (a) phagocytosis and antifungal activity against Candida albicans; (b) secretory pattern; and (c) levels of p38 phosphorylation.3. Unlike mock-treated controls, microglial cells exposed to TCA showed an increase in phagocytic activity. Unexpectedly, their capability to kill the ingested fungi significantly diminished. Moreover, TCA-treated cells produced amounts of macrophage inflammatory protein 1-alpha, tumor necrosis factor-alpha, and nitric oxide significantly higher than mock-treated cells. Finally, phosphorylation of p38 mitogen-activated protein kinase (MAPK) was detected in TCA-treated but not in mock-treated controls as early as 30 min after treatment.4. Overall, these results indicate that TCA causes a rapid molecular response in microglial cells, by the time, leading to an intriguing effector and secretory dysfunction.
Assuntos
Isquemia Encefálica/patologia , Citotoxicidade Imunológica , Hipóxia Encefálica/líquido cefalorraquidiano , Microglia/efeitos dos fármacos , Microglia/patologia , Linhagem Celular , Sobrevivência Celular , Citocinas/metabolismo , Formazans/farmacologia , Humanos , Microglia/metabolismo , Óxido Nítrico/metabolismo , Fagocitose , Sais de Tetrazólio/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Human herpesvirus-6 (HHV-6), a ubiquitous beta-herpesvirus, is the causative agent of roseola infantum and has been associated with a number of neurologic disorders including seizures, encephalitis/meningitis, and multiple sclerosis. Although the role of HHV-6 in human CNS disease remains to be fully defined, a number of studies have suggested that the CNS can be a site for persistent HHV-6 infection. OBJECTIVE: To characterize the extent and distribution of HHV-6 in human glial cells from surgical brain resections of patients with mesial temporal lobe epilepsy (MTLE). METHOD: Brain samples from eight patients with MTLE and seven patients with neocortical epilepsy (NE) undergoing surgical resection were quantitatively analyzed for the presence of HHV-6 DNA using a virus-specific real-time PCR assay. HHV-6 expression was also characterized by western blot analysis and in situ immunohistochemistry (IHC). In addition, HHV-6-reactive cells were analyzed for expression of glial fibrillary acidic protein (GFAP) by double immunofluorescence. RESULTS: DNA obtained from four of eight patients with MTLE had significantly elevated levels of HHV-6 as quantified by real-time PCR. HHV-6 was not amplified in any of the seven patients with NE undergoing surgery. The highest levels of HHV-6 were demonstrated in hippocampal sections (up to 23,079 copies/10(6) cells) and subtyped as HHV-6B. Expression of HHV-6 was confirmed by western blot analysis and IHC. HHV-6 was co-localized to GFAP-positive cells that morphologically appeared to be astrocytes. CONCLUSIONS: HHV-6B is present in brain specimens from a subset of patients with MTLE and localized to astrocytes in the absence of inflammation. The amplification of HHV-6 from hippocampal and temporal lobe astrocytes of MTLE warrants further investigation into the possible role of HHV-6 in the development of MTLE.
Assuntos
Encéfalo/virologia , Epilepsia do Lobo Temporal/virologia , Herpesvirus Humano 6/isolamento & purificação , Adolescente , Adulto , Antígenos Virais/análise , Antígenos Virais/imunologia , Western Blotting , Encéfalo/cirurgia , Criança , DNA Viral/análise , Proteínas de Ligação a DNA/análise , Epilepsia do Lobo Temporal/cirurgia , Feminino , Proteína Glial Fibrilar Ácida/análise , Proteína Glial Fibrilar Ácida/imunologia , Herpesvirus Humano 6/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neuroglia/química , Neuroglia/virologia , Lobo Temporal/virologia , Proteínas Virais/análiseRESUMO
We examined the association between risk of sporadic amyotrophic lateral sclerosis (ALS) and seroprevalence of antibodies to echovirus-7 (echo-7) and herpesviruses 6, 7, and 8 through a population-based case-control study. We enrolled in a northern Italy area 20 newly diagnosed ALS cases and 20 referents. Risk of ALS was higher in subjects seropositive for echo-7 when we used the immunofluorescent assay, while little increase was noted with the neutralization test. Considering the different characteristics of these two serological assays, these results suggest an association between disease risk and infection with enterovirus (EV) family members (not specifically echo-7). ALS risk was slightly associated with seropositivity of human herpesvirus-6 (odds ratio: 3.2; p = 0.102) and more strongly with human herpesvirus-8 seropositivity (odds ratio: 8.4; p = 0.064), though these point estimates were statistically unstable due to the limited number of observed cases. The findings of this study warrant further investigation in larger studies of the possible etiologic role of EV or herpesvirus infection in sporadic ALS.
Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Infecções por Echovirus/epidemiologia , Enterovirus Humano B , Infecções por Herpesviridae/epidemiologia , Herpesvirus Humano 6 , Herpesvirus Humano 7 , Herpesvirus Humano 8 , Infecções por Roseolovirus/epidemiologia , Estudos de Casos e Controles , Humanos , Itália/epidemiologia , Análise MultivariadaRESUMO
Herpesvirus infections can frequently lead to acute inflammation, yet the mechanisms regulating this event remain poorly understood. In order to determine some of the immunological mechanisms regulated by human herpesvirus infections, we studied the gene expression profile of lymphocytes infected with human herpesvirus 6 (HHV-6) by using a novel immunomicroarray. Our nylon-based immunomicroarray contained more than 1,150 immune response-related genes and was highly consistent between experiments. Experimentally, we found that independently of the HHV-6 strain used to infect T cells, multiple proinflammatory genes were increased and anti-inflammatory genes were decreased at the mRNA and protein levels. HHV-6 strains A and B increased expression of the genes for interleukin-18 (IL-18), the IL-2 receptor, members of the tumor necrosis factor alpha superfamily receptors, mitogen-activated protein kinase, and Janus kinase signaling proteins. As reported previously, CD4 protein levels were also increased significantly. Specific type 2 cytokines, including IL-10, its receptor, and IL-14, were downregulated by HHV-6 infection and, interestingly, amyloid precursor proteins and type 1 and 2 presenilins. Thus, T cells respond to HHV-6 infection by inducing a type 1 immune response that may play a significant role in the development and progression of diseases associated with HHV-6, including pediatric, hematologic, transplant, and neurologic disorders.
Assuntos
Perfilação da Expressão Gênica , Genes Virais , Herpesvirus Humano 6/genética , Linfócitos T/metabolismo , Sequência de Bases , Antígenos CD4/genética , Linhagem Celular , Primers do DNA , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Humanos , Interleucina-18/genética , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Linfócitos T/virologia , Regulação para CimaRESUMO
The antiviral and antiproliferative activity of new compounds having n-benzenesulphony 1-2 (2 or 3-pyridylethyl) benzimidazole as a base structure were studied in vitro. Their antitumour activity against human chronic myeloid leukaemia cells was evaluated and compared with that of equimolar doses of daunorubicin. Only compound 7a, with the presence of both the pyridyl moiety bound at the ethylenic bridge in C-2 of benzimidazole and the nitro-group in the benzene ring, displays a selective antiproliferative effect against certain leukaemia cells and a good antiviral activity especially towards the Coxsackie B5 virus. However, it should be noted that, in the case of hydroxybenzyl-benzimidazole, resistance also builds up to compound 7a, the Coxsackie B5 virus developing resistance to it after about ten runs. Cytotoxicity tests show that many of these substances are well tolerated by the VERO cells. The mechanism of action is still unclear.
Assuntos
Antineoplásicos/farmacologia , Antivirais/farmacologia , Benzimidazóis/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , Vírus/efeitos dos fármacos , Animais , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/patologia , Divisão Celular/efeitos dos fármacos , Chlorocebus aethiops , Daunorrubicina/farmacologia , Relação Dose-Resposta a Droga , Resistência Microbiana a Medicamentos , Enterovirus Humano B/efeitos dos fármacos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Células Vero/efeitos dos fármacosRESUMO
Routine search for herpesvirus types 1-5 by nested polymerase chain reaction revealed Epstein-Barr virus (EBV) DNA in the cerebrospinal fluid (CSF) of ten out of seventy-nine patients with human immunodeficiency virus (HIV) infection and central nervous system (CNS) disorders not associated with the presence of primary CNS lymphomas. One out of the ten CSF samples was positive for EBV DNA only, six were also positive for microbial agents of recognised neurological pathogenicity while the remaining three samples had a high content of HIV p24 Ag. When six available CSF samples out of the ten EBV DNA positive specimens were investigated for an intrathecal EBV antibody response, all six samples proved EBV antibody-free. The concurrent detection of neurotropic infectious agents and the absence of EBV antibodies in the CSF contribute to the uncertainty on the role of EBV in the neurological illness of the patients studied. One hypothesis considered is that the presence of EBV DNA in the CSF of a large fraction of the ten patients under study is an incidental event associated with EBV reactivation in the host's peripheral blood monocytes, but not related to the genesis of neurological disorders.
Assuntos
Doenças do Sistema Nervoso Central/virologia , DNA Viral/líquido cefalorraquidiano , Infecções por HIV/virologia , Herpesvirus Humano 4/isolamento & purificação , Doenças do Sistema Nervoso Central/complicações , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/complicações , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 4/genética , Humanos , Reação em Cadeia da Polimerase/métodos , Estudos RetrospectivosRESUMO
Some N-benzenesulphonyl-2(2- or 3-pyridylethyl)-benzimidazoles were synthesized and tested in vitro for antiproliferative and antiviral activity. Only one compound displayed a degree of antiproliferative activity against chronic myeloid leukaemia cells. However, a number of them exerted an antiviral effect at micromolar concentrations. The antiproliferative activity and the maximum potency of antiviral activity correlate with the presence of both the 2-pyridyl moiety bound at the ethylenic bridge in C-2 of benzimidazole and the nitro group in the benzene ring.
Assuntos
Antivirais/síntese química , Benzenossulfonatos/síntese química , Benzimidazóis/síntese química , Piridinas/síntese química , Animais , Antivirais/farmacologia , Benzenossulfonatos/farmacologia , Benzimidazóis/farmacologia , Divisão Celular/efeitos dos fármacos , Chlorocebus aethiops , Cromatografia em Camada Fina , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Espectroscopia de Ressonância Magnética , Piridinas/farmacologia , Células Tumorais Cultivadas , Células Vero , Ensaio de Placa Viral , Vírus/efeitos dos fármacosRESUMO
Herpes simplex virus 1 meningo-encephalitis was ascertained in a 63-year-old immunocompetent man. To determine the duration of the persistence of herpesvirus DNA in the central nervous system, the cerebrospinal fluid was periodically monitored by polymerase chain reaction for 53 days. In addition to HSV-1, Epstein-Barr virus DNA was detected in the cerebrospinal fluid 9 days after disease onset. The possible meaning of the Epstein-Barr virus DNA finding is discussed.
Assuntos
Encefalite Viral/líquido cefalorraquidiano , Infecções por Vírus Epstein-Barr/líquido cefalorraquidiano , Herpes Simples/líquido cefalorraquidiano , Herpesvirus Humano 1 , Herpesvirus Humano 4/genética , Imunocompetência , DNA Viral/análise , DNA Viral/líquido cefalorraquidiano , Encefalite Viral/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Herpes Simples/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Fifty four cerebrospinal fluid samples obtained from as many immunocomponent patients with disorders of the central nervous system were investigated for the presence of herpesvirus DNA by nested polymerase chain reaction in order to determine an etiological diagnosis. Four of these samples proved positive for the presence of Epstein-Barr virus DNA (7.4%). The result of this diagnostic study is reported to draw insiders' attention to the possible presence of EBV in cerebrospinal fluid from patients with central nervous system diseases.
Assuntos
Encefalopatias/virologia , DNA Viral/líquido cefalorraquidiano , Infecções por Herpesviridae/virologia , Herpesvirus Humano 4/isolamento & purificação , Adulto , Idoso , Encefalopatias/líquido cefalorraquidiano , Herpesviridae/genética , Herpesviridae/isolamento & purificação , Infecções por Herpesviridae/líquido cefalorraquidiano , Herpesvirus Humano 4/genética , Humanos , Imunocompetência , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
Some N-sulphonated-2-substituted benzimidazoles and imidazo[4,5-b]-pyridines were synthesized and tested in vitro for antiviral and antiproliferative activity. None of the compounds had antiviral properties. However, three of them inhibited the proliferation of leukaemia and lymphoma cell lines at micromolar concentrations. The maximum potency of antiproliferative activity is correlated with the presence of an ethylenic spacer between the two heterocycles.
Assuntos
Antineoplásicos/síntese química , Benzimidazóis/síntese química , Piridinas/síntese química , Antineoplásicos/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Benzenossulfonatos/síntese química , Benzenossulfonatos/farmacologia , Benzimidazóis/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Piridinas/farmacologia , Células Tumorais CultivadasRESUMO
A study was carried out to search for the presence of the seven human herpesvirus DNAs in cerebrospinal fluid from 52 human immunodeficiency virus-infected patients with brain disorders. Cytomegalovirus DNA was the most prevalent with 12 positive samples; Epstein-Barr virus and varicellazoster DNAs were detected in three and two samples, respectively, while no sample was positive for the DNA of the other herpesviruses.
Assuntos
Complexo AIDS Demência/líquido cefalorraquidiano , Complexo AIDS Demência/virologia , Infecções Oportunistas Relacionadas com a AIDS/líquido cefalorraquidiano , Citomegalovirus/isolamento & purificação , DNA Viral/líquido cefalorraquidiano , Infecções por Herpesviridae/líquido cefalorraquidiano , Herpesvirus Humano 3/isolamento & purificação , Herpesvirus Humano 4/isolamento & purificação , Complexo AIDS Demência/complicações , Infecções Oportunistas Relacionadas com a AIDS/virologia , Infecções por Citomegalovirus/líquido cefalorraquidiano , Infecções por Citomegalovirus/etiologia , Primers do DNA , Infecções por Herpesviridae/etiologia , Humanos , Reação em Cadeia da PolimeraseRESUMO
The association of a human herpesvirus 6 primary infection with a fatal case of hemophagocytic syndrome in a 3 month old baby is described. The trigger mechanism of the virus for the clinical syndrome is discussed.
Assuntos
Herpesvirus Humano 6/isolamento & purificação , Histiocitose de Células não Langerhans/diagnóstico , Animais , Anticorpos Antivirais/análise , Células Cultivadas , Chlorocebus aethiops , DNA Viral/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Fibroblastos , Herpesviridae/imunologia , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/imunologia , Histiocitose de Células não Langerhans/líquido cefalorraquidiano , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Lactente , Reação em Cadeia da Polimerase , Células VeroRESUMO
HepG2 cells, a well differentiated liver cell line, were shown to be permissive for both human herpesvirus 6 (HHV-6) A and B strains by three independent methods of analysis: detection of viral antigens, viral DNA sequences and infectious virus. HepG2 cell infection with HHV-6 resulted in functional damage as shown by the increased release in the culture medium of some hepatocyte markers. Cells surviving the acute infection were serially passaged without showing cytopathic effect, but, some months later, HHV-6 DNA was still present in the cells and virus induction with a phorbol ester was successful. A possible pathogenetic role of HHV-6 in liver diseases is discussed. Experiments of HepG2 infection with human herpesvirus 7 (HHV-7) were also carried out. The lack of an efficient virus replication suggested a difficulty for HHV-7 to infect hepatic cells.
Assuntos
Herpesvirus Humano 6/crescimento & desenvolvimento , Herpesvirus Humano 7/crescimento & desenvolvimento , Células Cultivadas , Efeito Citopatogênico Viral , DNA Viral/análise , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Sangue Fetal/citologia , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/metabolismo , Humanos , Células Tumorais Cultivadas , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
Virus isolation and viral DNA detection by the polymerase chain reaction were used to investigate the presence of human herpesvirus 6 (HHV-6) and human cytomegalovirus (HCMV) in bronchoalveolar lavage from 34 human immunodeficiency virus-1 (HIV-1)-infected patients with respiratory disorders. The aim was to assess the presence of reactivated HHV-6 in lung tissues for a subsequent evaluation of the frequency of virus involvement in respiratory clinical manifestations in the course of HIV-1 infection. Bronchoalveolar lavage samples were tested for the presence of HCMV, as a routine investigation within a protocol monitoring opportunistic infections in symptomatic HIV-1 patients. Whereas HCMV DNA was detected by the polymerase chain reaction in 12 bronchoalveolar lavage specimens, 10 of which were also positive for virus isolation, all samples were negative for HHV-6 by both virological procedures. The HHV-6 DNA finding in bronchoalveolar lavage from an HIV-1-seronegative patient with renal carcinoma, investigated accidentally together with the bronchoalveolar lavage specimens from HIV-1 seropositive patients, stressed the HHV-6 polymerase chain reaction-negative results in the bronchoalveolar lavage samples under study. It is concluded that the lung may be a target organ for HCMV infection in HIV-1-seropositive patients affected by respiratory symptoms but that this does not seem to be the case for HHV-6.
Assuntos
Líquido da Lavagem Broncoalveolar/virologia , Infecções por Citomegalovirus/virologia , Citomegalovirus/genética , DNA Viral , Soropositividade para HIV/complicações , Infecções por Herpesviridae/virologia , Herpesvirus Humano 6/genética , Estudos de Coortes , Citomegalovirus/imunologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/imunologia , Soropositividade para HIV/imunologia , HIV-1/isolamento & purificação , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/imunologia , Herpesvirus Humano 6/imunologia , HumanosRESUMO
A platinum(II) complex with the antiviral drug acyclovir was synthesized and its antiviral and anticancer properties were investigated in comparison to those of acyclovir and cisplatin. The platinum-acyclovir complex maintained the antiviral activity of the parent drug acyclovir, though showing a minor efficacy on a molar basis (ID(50) = 7.85 and 1.02 muMu for platinum-acyclovir and cisplatin, respectively). As anticancer agent, the platinum-acyclovir complex was markedly less potent than cisplatin on a mole-equivalent basis, but it was as effective as cisplatin when equitoxic dosages were administered in vivo to P388 leukaemia-bearing mice (%T/C = 209 and 211 for platinum-acyclovir and cisplatin, respectively). The platinum-acyclovir complex was also active against a cisplatin-resistant subline of the P388 leukaemia (%T/C = 140), thus suggesting a different mechanism of action. The DNA interaction properties (sequence specificity and interstrand cross-linking ability) of platinum-acyclovir were also investigated in comparison to those of cisplatin and [Pt(dien)Cl](+), an antitumour-inactive platinum-triamine compound. The results of this study point to a potential new drug endowed, at the same time, with antiviral and anticancer activity and characterized by DNA interaction properties different from those of cisplatin.
RESUMO
Papanicolaou (Pap)-stained cervical specimens from 160 squamous lesions were processed for the detection of human papillomavirus (HPV) DNA by an in situ hybridization (ISH) assay. Three biotinylated HPV DNA probes were employed, each containing HPV genotypes 6/11, HPV genotypes 16/18, or HPV genotypes 31/35/51. The HPV etiology of 86 lesions was ascertained (53.8%). In 74 out of 135 (58.8%) HPV-typed low-grade squamous intraepithelial lesions (SILs), HPV 6/11 was found in nine (6.6%), HPV 16/18 in 46 (34.2%), and HPV 31/35/51 in 19 lesions (14.1%); in 11 out of 18 HPV-typed high-grade SILs (61.1%), seven lesions (38.9%) were typed for HPV 16/18 and four (22.2%) for HPV 31/35/51. Of seven invasive carcinomas, only one (14.3%) reacted with the HPV 16/18 DNA probe. A cohort of 124 low-grade SILs were followed cytologically for a year. The results of this study are discussed in light of HPV type association and therapy.
Assuntos
Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Neoplasias do Colo do Útero/virologia , DNA Viral/análise , Feminino , Humanos , Hibridização In Situ , Neoplasias de Células Escamosas/terapia , Neoplasias de Células Escamosas/virologia , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/terapia , Displasia do Colo do Útero/terapia , Displasia do Colo do Útero/virologiaRESUMO
Forty-five sera from men with bladder cancer were examined in a micro solid-phase enzyme-linked immunosorbent assay (ELISA) and in a Western-blotting (WB) assay for the presence of IgG antibodies to papillomavirus (PV) genus-antigens of bovine origin. The ELISA detected PV antibodies in 75.6% of cancer patients. This antibody frequency was significantly higher than that found in both healthy males (22.7%) and patients with urological disorders (24%). A similar correlation among the PV antibody frequencies of the three groups was found with WB assay: 60% of the neoplastic group showed PV antibodies versus 17.3% in healthy males and 32.6% in non-neoplastic patients. Within the same group, 78% to 87% sera showed the same reactivity to both assays. Of these concordant sera, PV positive sera were 55.6% in cancer patients, 13.3% in healthy adults and 19.6% in patients with urological disorders. ELISA PV antibody level in the cancer group was higher than in each of the two control groups. The meaning of the humoral response to PV genus-antigens in men with bladder cancer is discussed.
Assuntos
Imunoglobulina G/sangue , Papillomaviridae/imunologia , Infecções por Papillomavirus/complicações , Infecções Tumorais por Vírus/complicações , Neoplasias da Bexiga Urinária/complicações , Adulto , Animais , Anticorpos Antivirais/sangue , Antígenos Virais de Tumores/imunologia , Western Blotting , Carcinoma Papilar/complicações , Carcinoma Papilar/imunologia , Bovinos , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/imunologia , Infecções Tumorais por Vírus/imunologia , Neoplasias da Bexiga Urinária/imunologia , Doenças Urológicas/complicações , Doenças Urológicas/imunologiaRESUMO
Virological studies were carried out on 3 to 36-month-old patients admitted to the Children's Hospital of the University of Modena with febrile syndrome from September 1990 to February 1991. Virological tests were carried out for human herpesvirus-6 (HHV-6), Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), adenoviruses, parainfluenza viruses 1, 2 and 3, respiratory syncytial virus (RSV) and influenza viruses A and B. Viral infections were confirmed in 60.7% patients: 39.6% were correlated with HHV-6, 5.4% with EBV, 5.4% with both HHV-6 and EBV, 5.4% with adenoviruses, 1.8% with HSV-1, 1.8% with CMV and 1.8% with an unidentified herpes-like lymphotropic virus. HHV-6 isolates were obtained from either peripheral blood lymphocytes (PBLs) or pharyngeal secretion of the infected children. HHV-6 infections included both primary infections (72%) and reactivations (28%). Among HHV-6 infected children, 40%, with exanthem subitum, had infections presenting serological evidence of primary infection and virus isolation from PBLs. The remaining cases of primary infection and the cases of reactivation were found in patients with febrile syndrome without rash (60%). HHV-6 isolates were obtained either from PBLs or pharyngeal secretions from these patients. Southern blot hybridization of the DNAs of 4 HHV-6 isolates showed that the circulating HHV-6 strains all appeared similar, but differed from the HHV-6 strain U1102 used as a positive control.
Assuntos
Infecções por Herpesviridae/microbiologia , Herpesvirus Humano 6/isolamento & purificação , Linfócitos/microbiologia , Faringe/microbiologia , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Pré-Escolar , Estudos de Coortes , Infecções por Herpesviridae/sangue , Infecções por Herpesviridae/epidemiologia , Humanos , Lactente , Itália/epidemiologiaRESUMO
Nalidixic acid and oxolinic acid, two antibacterial agents known to inhibit bacterial DNA gyrase, are shown to suppress the replication, as well as the cytopathic effect, of BK virus in Vero cell cultures. The inhibition of virus replication was detectable at day 4 post infection in cultures which had been continuously exposed to drugs at concentrations as low as 0.02 to 0.04 mM of nalidixic acid and 0.2 mM of oxolinic acid. These active concentrations are inferior to plasma levels attained in the course of clinical use of the drugs for antibacterial chemotherapy. Also, under these circumstances, no cytotoxicity occurred. The inhibition of development of cytopathology and of virus-induced cell death was demonstrable in cultures treated for 12 days with the drugs. Under these circumstances of prolonged action, oxolinic acid proved to be slightly cytotoxic in that virus inhibitory doses reduced the viability of normal cells. No alterations in the topological conformation of the viral genome or accumulation of end products of viral DNA replication were detected. However, accumulation of viral DNA form I at 48 h post infection suggests that the drugs act through a mechanism involving DNA topoisomerase.
Assuntos
Vírus BK/efeitos dos fármacos , Ácido Nalidíxico/farmacologia , Ácido Oxolínico/farmacologia , Polyomavirus/efeitos dos fármacos , Inibidores da Topoisomerase II , Replicação Viral/efeitos dos fármacos , Antígenos Virais/biossíntese , Efeito Citopatogênico Viral , DNA Viral/biossínteseRESUMO
Thirty-three sera from women symptom-free for papillomatous disease and 27 sera from women with flat or exophytic genital warts were examined for the presence of IgG and IgM antibodies to papillomavirus (PV) genus-antigens. For this purpose, sera were challenged with genus-antigens extracted from both human and bovine purified virions of PVs, in a micro solid-phase enzyme-linked immunosorbent assay (ELISA). The assay performed with PV genus-antigens of human origin showed that in women with genital warts, IgG antibodies were present in a percentage of 70.37% and IgM antibodies in a percentage of 40.74%; in apparently uninfected women, IgG and IgM antibodies were present in a percentage of 54.54% and 24.24% respectively. When sera were challenged with PV genus-antigens of bovine origin for IgG antibody class, positivity was 70.37% in women with genital disease and 45.45% in symptom-free women. IgG and IgM antibody response in women with and without papillomatous genital lesions is discussed.