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Biomedical subjects

Tapani Hovi

Publications and source records attributed to Tapani Hovi.

At least 19 recordsLinked to original sources

Serum antibody response to periodontal pathogens and herpes simplex virus in relation to classic risk factors of cardiovascular disease.

BACKGROUND: Increasing evidence links chronic infections, especially burden of several infections, with increased risk for cardiovascular diseases (CVD). We studied joint immune response against two major periodontal pathogens and herpes simplex virus (HSV) in relation to established risk factors of CVD. METHODS: Serum antibody levels to HSV, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were determined by ELISA. The study included 1107 subjects, 734 from Finland and 373 from Russia. RESULTS: Combined antibody response to periodontal pathogens was associated inversely (OR, 95% CI) with high-density lipoprotein (HDL) cholesterol concentration (beta = 0.35; 0.20, 0.60; P < 0.001) and directly with HSV antibody quartiles: compared with the first quartile, ORs (95% CI) for quartiles 2-4 were 1.43 (0.88-2.32), 1.74 (1.07-2.82), and 1.89 (1.18-3.02), respectively (P for trend <0.001), after adjusting for age, gender, area, education, smoking, BMI, alcohol, triglycerides, and number of teeth. In linear regression analysis, the 3-pathogen antibody score (comprising antibody levels against periodontal pathogens and HSV) was inversely associated with HDL cholesterol concentration (beta = -0.067/1 mmol/l; -0.235, -0.018; P < 0.05). CONCLUSIONS: HSV infection may promote infection by periodontal pathogens. Furthermore, the infectious burden comprising HSV and periodontitis may increase the risk for CVD by clearly decreasing HDL cholesterol concentrations.

Adult↗

Surveillance for polioviruses.

Clinical case-driven surveillance for poliovirus remains the cornerstone of monitoring the progress of the poliomyelitis eradication initiative (PEI). It includes notification and careful investigation of cases of acute flaccid paralysis (AFP), timely collection of stool specimens from the patient, and virological examination of the specimens in an accredited laboratory. Successful high quality APF surveillance requires painstaking perseverance and smooth interplay of several different groups of health care workers in a country. Environmental surveillance (ES) may in certain situations be more sensitive than AFP surveillance in detecting wild type poliovirus or vaccine derived poliovirus circulation. However, apart from being highly labour intensive, it cannot be optimally applied in large parts of the world because of the lack of converging sewage systems. Under these conditions, the very rationale of ES, examining of individual samples representing large groups (hundreds of thousands) of people cannot be readily exploited. Whatever approach of poliovirus surveillance is used, we will always be monitoring subgroups of potential poliovirus excreting people only. Therefore, several years long poliovirus-free monitoring period is needed to confirm that poliovirus transmission has stopped in a given population.

Humans↗

Viral upper respiratory tract infections in young children with emphasis on acute otitis media.

Viral upper respiratory infection is the most common reason for seeking medical care for children. Recurrent viral respiratory infections and subsequent complications (e.g. acute otitis media (AOM)) are a burden for children, their families and society. Over the past decade, our knowledge on the significance of respiratory viruses has broadened remarkably. Viruses cause large variety of respiratory diseases and cause alone diseases, which previously have been assumed to be bacterial only (e.g. AOM and pneumonia). Methods for detection analysis of respiratory viruses are developing making both the diagnosis and epidemiological investigations of respiratory infections easier. Accurate diagnosis of respiratory infections and awareness of possible viral etiology could reduce the use of antibiotics. Etiologic studies of viral infections are becoming increasingly important, with the emergence of new antiviral drugs and vaccines.

Acute Disease↗

Alignment of capsid protein VP1 sequences of all human rhinovirus prototype strains: conserved motifs and functional domains.

An alignment was made of the deduced amino acid sequences of the entire capsid protein VP1 of all human rhinovirus (HRV) prototype strains to examine conserved motifs in the primary structure. A set of previously proposed crucially important amino acids in the footprints of the two known receptor molecules was not conserved in a receptor group-specific way. In contrast, VP1 and VP3 amino acids in the minor receptor-group strains corresponding to most of the predicted ICAM-1 footprint definitely differed from those of the ICAM-1-using major receptor-group strains. Previous antiviral-sensitivity classification showed an almost-complete agreement with the species classification and a fair correlation with amino acids aligning in the antiviral pocket. It was concluded that systematic alignment of sequences of related virus strains can be used to test hypotheses derived from molecular studies of individual model viruses and to generate ideas for future studies on virus structure and replication.

Capsid↗

Containment of polioviruses after eradication and OPV cessation: characterizing risks to improve management.

The goal of the World Health Organization is to stop routine use of oral poliovirus vaccine shortly after interruption of wild poliovirus transmission. A key component of this goal is to minimize the risk of reintroduction by destruction of polioviruses except in an absolute minimum number of facilities that serve essential functions and implement effective containment. Effective containment begins with a complete facility risk assessment. This article focuses on characterizing the risks of exposure to polioviruses from the essential vaccine production, quality control, and international reference and research facilities that remain. We consider the potential exposure pathways that might lead to a poliovirus reintroduction, including para-occupational exposures and releases to the environment, and review the literature to provide available estimates and a qualitative assessment of containment risks. Minimizing the risk of poliovirus transmission from a poliovirus facility to increasingly susceptible communities is a crucial and ongoing effort requiring understanding and actively managing the potential exposure pathways.

Containment of Biohazards↗

Rhinovirus/enterovirus RNA in tonsillar tissue of children with tonsillar disease.

BACKGROUND: Human rhinoviruses (HRVs) together with the closely related human enteroviruses (HEVs) cause most of the acute respiratory illnesses throughout the year. HRVs have been detected in most parts of the respiratory tract but not in pharyngeal tonsils. OBJECTIVES: We aimed to find out whether HRVs were detectable in tonsillar tissue and if their presence correlated to the tonsillar disease. STUDY DESIGN: Thirty-three tonsillar samples collected in February-March 2003 from children with no acute respiratory symptoms were studied with HRV in situ hybridization (HRV-ISH). Ten tonsillar samples were further examined in a separate laboratory by two different reverse transcription polymerase chain reaction (RT-PCR) methods designed for detection of HRV/HEV RNA. RESULTS: Twenty of the 33 samples (62%) were positive by HRV-ISH. Five positive and five negative HRV-ISH samples were investigated by two different PCR methods. HRV/HEV RNA was detected in 9 of the 10 specimens by a hanging drop-nested PCR. One HRV-ISH negative sample was positive by a conventional non-nested PCR. One of the samples studied by all three methods, from a patient with recurrent tonsillitis, had no detectable HRV/HEV RNA. Positive result in HRV-ISH did not correlate significantly with underlying tonsillar disease, history of respiratory infections or bronchial asthma. Altogether HRV/HEV RNA was detected in 75% of the tonsils with no correlation to patients' operation indication or history of respiratory diseases. CONCLUSIONS: In February-March, HRV/HEV RNA was frequently found in tonsillar tissue in children irrespective of the tonsillar pathology. Whether detection of the RNA is a marker of chronic infection or is merely remnant of past infection is not known.

Adolescent↗

Presence of viral and bacterial pathogens in the nasopharynx of otitis-prone children. A prospective study.

OBJECTIVE: The purpose of the present study was to examine and follow up the presence of respiratory viral and bacterial pathogens in the nasopharynx of otitis-prone children during the cold season and compare the findings with the child's respiratory symptoms. METHODS: We enrolled 121 otitis-prone children, aged 10 months to 4 years for a prospective study. The nasopharyngeal swab (NPS) were studied at the baseline and after 12 and 24 weeks for respiratory viruses and at the baseline and after 24 weeks for bacteria. Presence of picorna(rhino-entero-parecho)-, influenza-, adenoviruses and Mycoplasma pneumoniae was detected by PCR. NPS specimens were cultured for Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Clinical data (the rate of respiratory symptom days, otitis media, tympanometry findings, day-care attendance and the number of siblings) were compared with microbiological data. RESULTS: Rhinovirus was found in 30% of the samples at the baseline, in 8% and in 19% of the samples after 12 and 24 weeks, respectively. Enterovirus was detected in 19% of the samples, in 21% and in 12% of samples after 12 and 24 weeks, respectively. Picornavirus positivity correlated with the respiratory symptoms but not with the number of otitis media or with abnormal tympanometry. Two samples were adeno- and three samples influenzavirus positive. Parechovirus and M. pneumoniae were negative in all samples. Rhinovirus positivity correlated with that of M. catarrhalis and S. pneumonia but not with H. influenzae. Microbiological positivity was not significantly associated with the type of day-care. CONCLUSIONS: Picornaviruses as well as bacteria were commonly found in the nasopharynx of otitis-prone children during the cold season, even in the absence of clinical symptoms.

Bacteria↗

A whole cell immunization-derived monoclonal antibody that protects cells from coxsackievirus A9 infection binds to both cell surface and virions.

Coxsackievirus A9 (CAV-9) infects human rhabdomyosarcoma (RD) cells using an unidentified RGD-independent receptor. Monoclonal antibodies were prepared by immunizing mice with intact RD cells and by selecting cells from the cytopathic effect of CAV-9 for protection. Here we describe a monoclonal antibody that binds to host cell plasma membrane and protects cells from virus infection. In addition, binding of the virus to cell monolayers was more efficient in the presence of the antibody, suggesting that the antibody is also capable of recognizing virus particles. Immunoprecipitation and electron microscopy studies with highly purified virus preparations verified binding of the monoclonal antibody to the virus particles. The antibody also recognized coxsackievirus A21 and all three serotypes of poliovirus, but without affecting their infectivity. The amino acid sequence of CAV-9 recognized by the monoclonal antibody was identified by peptide mapping and by producing escape mutants in the presence of the antibody.

Amino Acid Sequence↗

Is there any specific association between respiratory viruses and bacteria in acute otitis media of young children?

BACKGROUND: Respiratory viral infections are usually preceding or coinciding with acute otitis media (AOM) in children. It is not known if a given viral infection would facilitate invasion of bacterial pathogens into the middle ear in a species-specific way. We reanalysed the microbiological results of the two prospective Finnish Otitis Media (FinOM) studies for this purpose. METHODS: The children had been followed from 2 months to 2 years of age in specific study clinics and all referred AOM events were analysed. Combined results of virus detection tests from middle ear fluid and nasopharyngeal aspirate and those of bacterial culture from middle ear fluid were cross-tabulated for 529 AOM events in the FinOM Cohort Study and for 364 events in the FinOM Vaccine Trial. RESULTS: In both studies the main bacterial pathogens were Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis while the main viruses detected were rhinoviruses and respiratory syncytial virus (plus enteroviruses in the Vaccine Trial). No distinct species-specific associations were observed between the viral and bacterial findings. CONCLUSION: We did not find support to the theory that respiratory infection caused by a given viral species would favour growth of a certain bacterial pathogen in the MEF more than another.

Bacterial Infections↗

Genetic diversity of JC virus in the Saami and the Finns: implications for their population history.

The JC virus (JCV) genotyping method was used to gain insights into the population history of the Saami and the Finns, both speaking Finno-Ugric languages and living in close geographic proximity. Urine samples from Saami and Finns, collected in northern and southern Finland, respectively, were used to amplify a 610-bp JCV-DNA region containing abundant type-specific mutations. Based on restriction site polymorphisms in the amplified fragments, we classified JCV isolates into one of the three superclusters of JCV, type A, B, or C. All 15 Saami isolates analyzed and 41 of 43 Finnish isolates analyzed were classified as type A, the European type, and two samples from Finns were classified as type B, the African/Asian type. We then amplified and sequenced a 583-bp JCV-DNA region from the type A isolates of Saami and Finns. According to type-determining nucleotides within the region, we classified type A isolates into EU-a1, -a2, or -b. Most type A isolates from Saami were classified as EU-a1, while type A isolates from Finns were distributed among EU-a1, EU-a2, and EU-b. This trend in the JCV-genotype distribution was statistically significant. On a phylogenetic tree based on complete sequences, most of the type A isolates from Saami were clustered in a single clade within EU-a1, while those from Finns were distributed throughout EU-a1, EU-a2, and EU-b. These findings are discussed in the context of the population history of the Saami and the Finns. This study provides new complete JCV DNA sequences derived from populations of anthropological interest.

Adult↗

Phenotypic and genetic changes in coxsackievirus B5 following repeated passage in mouse pancreas in vivo.

Common enterovirus infections appear to initiate or facilitate the pathogenetic processes leading to type 1 diabetes, and also sometimes precipitate the clinical disease. In experimental infection of mice, coxsackieviruses have shown to have a strong affinity for the exocrine tissue, while even in lethal cases, the islets remain unaffected. The virus strain most intensively studied in this respect is the diabetogenic variant E2 of coxsackievirus B4. In addition, it is known that all six serotypes of coxsackie B viruses can be made diabetogenic by repeated passages in either mouse pancreas in vivo or in cultured mouse beta-cells in vitro. However, the genetic determinants of the phenomenon have not been determined. In the present study, a laboratory strain of coxsackievirus B5 was passaged repeatedly in mouse pancreas in vivo. After 15 passages, the virus phenotype was clearly changed and infection of the variant resulted in a diabetes-like syndrome in mice characterized by chronic pancreatic inflammation together with dysregulation in glucose metabolism, loss of pancreatic acinar tissue, and mild insulitis. In order to characterize the genetic determinants involved in mouse pancreas adaptation, the passaged virus variant together with the parental virus strain was cloned for molecular characterization. The whole genome sequencing of both virus strains revealed only limited differences. Altogether, eight nucleotides were changed resulting in five amino acid substitutions, of which three were located in the capsid proteins.

Animals↗

Environmental surveillance of wild poliovirus circulation in Egypt--balancing between detection sensitivity and workload.

Examination of sewage specimens for poliovirus (environmental surveillance) was adopted as a supplementary tool in the surveillance of poliomyelitis in Egypt. Sewage samples were concentrated about 50-fold using a simple two-phase separation technique, and inoculated in cell cultures in two collaborating laboratories in parallel. All but 9 of the 293 (97%) samples collected from January 2001 to December 2002 contained poliovirus and/or other enteroviruses, with polioviruses being detected in 84% of the samples. The proportion of specimens containing type 1 wild poliovirus (PV1W, the North-East African (NEAF) genotype) was less in 2002 (16%) than in 2001 (57%), and further decreased in 2003. While the overall sensitivity to detect PV1W was similar in the two collaborating laboratories, the specimens scored positive were not identical. Parallel cultures inoculated with aliquots of a given specimen very frequently resulted in isolation of different viruses. Moreover, partial sequence analysis occasionally revealed representatives of different genetic lineages of PV1W in a given specimen. These results emphasize the need to use intensive laboratory analysis to optimise sample sensitivity in environmental poliovirus surveillance, and the difficulties in reproducing the isolation results by simple re-inoculation of samples containing a mixture of different viruses.

Animals↗

Phylogenetic analysis of human rhinovirus capsid protein VP1 and 2A protease coding sequences confirms shared genus-like relationships with human enteroviruses.

Phylogenetic analysis of the capsid protein VP1 coding sequences of all 101 human rhinovirus (HRV) prototype strains revealed two major genetic clusters, similar to that of the previously reported VP4/VP2 coding sequences, representing the established two species, Human rhinovirus A (HRV-A) and Human rhinovirus B (HRV-B). Pairwise nucleotide identities varied from 61 to 98 % within and from 46 to 55 % between the two HRV species. Interserotypic sequence identities in both HRV species were more variable than those within any Human enterovirus (HEV) species in the same family. This means that unequivocal serotype identification by VP1 sequence analysis used for HEV strains may not always be possible for HRV isolates. On the other hand, a comprehensive insight into the relationships between VP1 and partial 2A sequences of HRV and HEV revealed a genus-like situation. Distribution of pairwise nucleotide identity values between these genera varied from 41 to 54 % in the VP1 coding region, similar to those between heterologous members of the two HRV species. Alignment of the deduced amino acid sequences revealed more fully conserved amino acid residues between HRV-B and polioviruses than between the two HRV species. In phylogenetic trees, where all HRVs and representatives from all HEV species were included, the two HRV species did not cluster together but behaved like members of the same genus as the HEVs. In conclusion, from a phylogenetic point of view, there are no good reasons to keep these two human picornavirus genera taxonomically separated.

Cysteine Endopeptidases↗

The minor receptor group of human rhinovirus (HRV) includes HRV23 and HRV25, but the presence of a lysine in the VP1 HI loop is not sufficient for receptor binding.

Like all 10 minor receptor group human rhinoviruses (HRVs), HRV23 and HRV25, previously classified as major group viruses, are neutralized by maltose binding protein (MBP)-V33333 (a soluble recombinant concatemer of five copies of repeat 3 of the very-low-density lipoprotein receptor fused to MBP), bind to low-density lipoprotein receptor in virus overlay blots, and replicate in intercellular adhesion molecule 1 (ICAM-1)-negative COS-7 cells. From phylogenetic analysis of capsid protein VP1-coding sequences, they are also known to cluster together with other minor group strains. Therefore, they belong to the minor group; there are now 12 minor group and 87 major group HRV serotypes. Sequence comparison of the VP1 capsid proteins of all HRVs revealed that the lysine in the HI loop, strictly conserved in the 12 minor group HRVs, is also present in 9 major group serotypes that are neutralized by soluble ICAM-1. Despite the presence of this lysine, they are not neutralized by MBP-V33333 and fail to replicate in COS-7 cells and in HeLa cells in the presence of an ICAM-1-blocking antibody. These nine serotypes are therefore "true" major group viruses.

Amino Acid Sequence↗

Presence of specific viruses in the middle ear fluids and respiratory secretions of young children with acute otitis media.

The purpose of the study was to investigate the presence of different viruses in middle ear fluids and nasopharyngeal aspirates in young children with acute otitis media. Two cohorts of children (N = 329 and 611) were followed from 2 to 24 months of age in Finland in two prospective studies (Finnish Otitis Media Cohort Study and Finnish Otitis Media Vaccine Trial). During the study period, nasopharyngeal and middle ear fluid specimens for each acute otitis media event were examined for eight (Cohort Study) or ten (Vaccine Trial) common respiratory viruses; adenoviruses, influenza viruses A and B, parainfluenza viruses 1, 2, and 3, respiratory syncytial virus (RSV), enteroviruses, parechoviruses, and rhinoviruses. Picornaviruses (rhinoviruses, enteroviruses, and parechoviruses) were determined by reverse transcription PCR while antigen detection was used for the other viruses. A virus was present in either nasopharyngeal or middle ear specimen in 54% of events in the first cohort and in 67% of events in the second. Rhinoviruses formed the most common virus group detected (41-32%), followed by enteroviruses (25%, sought in the second cohort only) and respiratory syncytial virus (RSV) (10%). All the other viruses represented jointly 8-10% of the events. In conclusion, using the methods described in this study, a specific virus infection was diagnosed in two thirds of all acute otitis media events in young children. Picornavirus RNA was detected in association with more than a half of all acute otitis media events. The use of PCR-based methods for the other respiratory viruses might have increased further the overall virus detection rate in acute otitis media.

Acute Disease↗

Mechanisms of beta cell death during restricted and unrestricted enterovirus infection.

Coxsackie B virus (CVB-5) infections potentially trigger and accelerate pancreatic beta cell damage leading to type 1 diabetes. In vivo, all viruses face natural resistance mediated by various host factors which restrict the progression of infection. Thus, the aims of this study were to generate a tissue culture model of restricted coxsackie B virus infection in primary islet cells by preventing the production of viral progeny with a selective inhibitor of viral RNA replication and to investigate the mechanisms of virus-induced islet cell death during productive and restricted infective conditions. Cultured foetal porcine islet cells were infected effectively with the prototype strain of coxsackievirus B5 (CVB-5). Nuclear viability stainings and electron microscopy showed productive infection to result in dominantly necrotic cell death with additional slight induction of apoptosis during the 7 days of follow-up. The restricted conditions were created by addition of guanidine-hydrochloride (G-HCl) into culture medium. At 1 mM concentration, it significantly protected the infected cells from necrosis and thus maintained high viability. This was associated with increased significantly apoptosis. In perifusion analysis, the cellular ability to release insulin was reduced, although the metabolic integrity was preserved as shown by MTT-analysis and cellular ATP levels. These data show that restriction of CVB-5 replication with G-HCl protects islet cells against virus-induced necrosis. However, restriction of viral replication shifts the mechanism of cell death from necrosis toward apoptosis. A slowly progressing subclinical infection of islets could thus lead to increased beta-cell apoptosis.

Adenosine Triphosphate↗