Biomedical subjects

L Kinnunen

Publications and source records attributed to L Kinnunen.

At least 19 recordsLinked to original sources

PubMed2002

HLA-patterns in patients with multiple sclerosis and type I diabetes mellitus: evidence for possible mutual exclusion of both diseases.

BACKGROUND: Type I diabetes mellitus (T1DM) and multiple sclerosis (MS), both immune-mediated diseases, rarely co-exist in the same individual or co-segregate in families. HLA susceptibility genes for T1DM (DRB1*0401, DRB1*0404, DQB1*0302, DRB1*0301, DQB1*0201) rarely occur in MS patients. HLA genes known to confer "resistance" to T1DM (DRB1*1501, DQB1*0602-DQA1*0102) predispose to MS. To test the hypothesis of mutually exclusive HLA patterns, patients affected by T1DM plus MS were compared to those of patients affected by either of the diseases alone in a case-control study. METHODS: Blood was sampled for analysis of HLA class I and class II alleles from 66 patients of German ancestry, of whom 33 had T1DM plus MS, and 33 had MS-only. For comparison to patients with T1 DM-only we referred to published data. HLA typing was performed using conventional serology (immuno-magnetic beads) and genotyping (SSP-PCR Dynal(R) SSP low/high resolution kits). RESULTS: Individuals with co-existing MS plus T1DM displayed the expected T1DM associated HLA-pattern (75.8% carried DRB1*04, 69.7% carried DQB1*0302, 42% were DR4, DR3 heterozygous), but failed to display the expected MS associated HLA-pattern (0% carried DQB1*0602, 3.1% carried DQA1*0102). The expected MS associated HLA-pattern of Caucasoid patients, however, was found in the MS-only patients (42% carried DRB1*1501-DQB1*0602, 58% carried DQA1*0102), while the prevalence of T1DM susceptibility and 'resistance' alleles was not different from the general population. The allele frequency of DRB1*1501 was 16/66, 24.2% in the 33 MS-only patients, and 0% in the 33 MS plus T1DM patients. The allele frequency of DQB1*0602 was 16/66, 24.2% in the 33 MS-only patients, and 0% in the 33 MS plus T1DM patients. The allele frequency of DQA1*0102 was 18/66, 27.3%, in the 33 MS-only patients, and 1/66 1.5% in the 33 MS plus T1DM patients. CONCLUSION: These data confirm the hypothesis of mutually exclusive HLA-patterns of T1DM and MS, and are consistent with a low rate of co-morbidity of both diseases.

Adolescent↗

PubMed2001

Acceptable protective efficacy of influenza vaccination in young military conscripts under circumstances of incomplete antigenic and genetic match.

Commercial inactivated parenteral influenza vaccines reduced febrile (> or = 38 degrees C) respiratory illness by 53% (95% CL: 41-63%) during a 3 week outbreak in 1998 when A/Sydney/5/97(H3N2)-like influenza viruses were shown to be the predominant etiological agents and an older antigenic variant, A/Nanchang/933/95, served as the vaccine virus. The calculatory efficacy for preventing virologically diagnosed influenza infections was 57% (95% CL: 40-68%). The study population consisted of 1374 young male military conscripts. Vaccination coverage on a voluntary basis was 67%. Vaccination was ineffective in preventing febrile illness during a second epidemic wave lasting 2 weeks when mainly adenoviruses were shown to have been circulating in the garrison. Out of the 36 nasopharyngeal aspirates positive for influenza A by antigen detection, 18 A/Sydney/5/97-like strains (10 from non-vaccinated and eight from vaccinated subjects) and two A/Nanchang/933/95-like strains (both from non-vaccinated subjects) were isolated in MDCK cell cultures. Intraepidemic variation was detected among the A/Sydney/5/97-like field strains in their HA1 sequences and reactivity in HI tests, but no evidence was obtained that this variation would have been of significance to the virus in breaking through the vaccination-induced immunity.

Adult↗

PubMed2001

Arginine/lysine-rich structural element is involved in interferon-induced nuclear import of STATs.

Signal transducers and activators of transcription (STATs) are latent cytoplasmic transcription factors, which mediate interferon (IFN), interleukin, and some growth factor and peptide hormone signaling in cells. IFN stimulation results in tyrosine phosphorylation, dimerization, and nuclear import of STATs. In response to IFN-gamma stimulation, STAT1 forms homodimers, whereas IFN-alpha induction results in the formation of STAT1.STAT2 heterodimers, which assemble with p48 protein in the nucleus. Phosphorylation as such is not sufficient to target STATs into the nucleus; rather, the dimerization triggered by phosphorylation is essential. Although IFN-induced nuclear import of STATs is mediated by the importin/Ran transport system, no classic nuclear localization signal (NLS) has been found in STATs. In the three-dimensional structure of STAT1, we observed a structural arginine/lysine-rich element within the DNA-binding domain of the molecule. We created a series of point mutations in these elements of STAT1 and STAT2 and showed by transient transfection/IFN stimulation assay that this site is essential for the nuclear import of both STAT1 and STAT2. The results suggest that two arginine/lysine-rich elements, one in each STAT monomer, are required for IFN-induced nuclear import of STAT dimers. Import-defective STAT1 and STAT2 proteins were readily phosphorylated and dimerized, but they functioned as dominant negative molecules inhibiting the nuclear import of heterologous STAT protein.

Amino Acid Sequence↗

PubMed2001

Phylogenetic analysis of avian paramyxovirus 1 strains isolated in Finland.

Eight strains of avian paramyxovirus type 1 (PMV-1) isolated in Finland during the last 3 decades were studied with reverse transcriptase polymerase chain reaction (RT-PCR) and subsequent sequence analysis of the region of 208 nucleotides covering the fusion (F) protein cleavage site. Both genetic and antigenic heterogeneity of the strains was significant. Direct epidemiological links between strains isolated during successive outbreaks, and also between strains isolated from wild fauna and from poultry or captive birds, were seen in this study. These results also support the previously published view that wild waterfowl serve as a reservoir for the apathogenic or low-pathogenic strains, allowing them to evolve further into pathogenic strains.

Amino Acid Sequence↗

PubMed2000

Molecular epidemiology and evolution of coxsackievirus A9.

Genetic relationships between 35 clinical isolates of coxsackievirus A9 (CAV9), collected during the last five decades from different geographical regions, were investigated by partial sequencing. Analysis of a 150 nucleotide sequence at the VP1/2A junction region identified 12 CAV9 genotypes. While most of the strains within each genotype showed geographical clustering, the analysis also provided evidence for long-range importation of virus strains. Phylogenetic analysis of a longer region around the VP1/2A junction (approximately 390 nucleotides) revealed that the designated genotypes actually represented phylogenetic lineages. The phylogenetic grouping pattern of the isolates in the analysis of the VP4/VP2 region was similar to that obtained in the VP1/2A region whereas analysis of the 3D region indicated a strikingly different grouping, which suggests that recombination events may occur in the region encoding the nonstructural proteins. Analysis of the deduced amino acid sequences of the VP1 polypeptide demonstrated that the RGD (arginine-glycine-aspartic acid) motif, implicated in the interaction of the virus with integrin, was fully conserved among the isolates.

Amino Acid Motifs↗

PubMed1999

A new picornavirus isolated from bank voles (Clethrionomys glareolus).

A previously unknown picornavirus was isolated from bank voles (Clethrionomys glareolus). Electron microscopy images and sequence data of the prototype isolate, named Ljungan virus, showed that it is a picornavirus. The amino acid sequences of predicted Ljungan virus capsid proteins VP2 and VP3 were closely related to the human pathogen echovirus 22 (approximately 70% similarity). A partial 5' noncoding region sequence of Ljungan virus showed the highest degree of relatedness to cardioviruses. Two additional isolates were serologically and molecularly related to the prototype.

Amino Acid Sequence↗

PubMed1999

Relationships between simian and human enteroviruses.

Partial sequences from two genomic regions of simian enteroviruses were analysed and their relatedness to other picornaviruses was compared. Of the 18 simian viruses included in the analysis, sequences were obtained from eleven strains for at least one genomic region. In the 5' non-coding region, SV6, SV19, SV26, SV35, SV43 and SV46 (simian viruses) and BA13 (baboon virus) clearly grouped together with human enteroviruses, whereas SV4, SV28 and SA4 (South African isolate) were more distantly related. In the 3D RNA polymerase-coding region, SV26, SV35, SV43 and SV46 could be clearly identified as enteroviruses and fell into the previously defined cluster A, which contains such human viruses as coxsackievirus A16 and enterovirus 71. However, although SV6 and BA13 were also enterovirus-like, they did not belong to any known genetic cluster of human enteroviruses. Moreover, while SV18 could be recognized as a picornavirus, it did not directly group with members of the genus Enterovirus.

5' Untranslated Regions↗

PubMed1999

Evidence of recombination among enteroviruses.

Human enteroviruses consist of more than 60 serotypes, reflecting a wide range of evolutionary divergence. They have been genetically classified into four clusters on the basis of sequence homology in the coding region of the single-stranded RNA genome. To explore further the genetic relationships between human enteroviruses and to characterize the evolutionary mechanisms responsible for variation, previously sequenced genomes were subjected to detailed comparison. Bootstrap and genetic similarity analyses were used to systematically scan the alignments of complete genomic sequences. Bootstrap analysis provided evidence from an early recombination event at the junction of the 5' noncoding and coding regions of the progenitors of the current clusters. Analysis within the genetic clusters indicated that enterovirus prototype strains include intraspecies recombinants. Recombination breakpoints were detected in all genomic regions except the capsid protein coding region. Our results suggest that recombination is a significant and relatively frequent mechanism in the evolution of enterovirus genomes.

Enterovirus↗

PubMed1998

Foodborne outbreaks of hepatitis A in a low endemic country: an emerging problem?

This paper describes 2 outbreaks of hepatitis A infection in Finland, a very low endemic area of hepatitis A infection, where a large proportion of the population is now susceptible to infection by hepatitis A virus (HAV). The first outbreak involved people attending several schools and day-care centres; the second employees of several bank branches in a different city. The initial investigation revealed that both were related to food distributed widely from separate central kitchens. Two separate case-control studies implicated imported salad food items as the most likely vehicle of infection. HAV was detected in the stool of cases from both outbreaks using reverse-transcriptase polymerase chain reaction; however, comparison of viral genome sequences proved that the viruses were of different origin and hence the outbreaks, although occurring simultaneously, were not linked. Foodborne outbreaks of HAV may represent an increasing problem in populations not immune to HAV.

Adolescent↗

PubMed1996

HA1 domain of influenza A (H3N2) viruses in Finland in 1989-1995: evolution, egg-adaptation and relationship to vaccine strains.

The HA1 gene sequences of 22 MDCK cell-derived influenza A (H3N2) strains, ten of their egg-derived counterparts and three vaccine strains were determined. Antigenic and sequence differences between the epidemic and vaccine strains were recorded, most striking in 1992/93; a minority of the amino acid differences in 1989-95 was involved in egg-adaptation. Changes in the assortment of amino acid substitutions produced during egg-adaptation of field strains may account for the difficulty encountered in isolating these viruses in embryonated eggs. Six revertant amino acids, characteristic of field strains prevalent in 1969-71 were recorded in 1994/95. Their genome sequence was interpreted to have been maintained over the interval years among low abundant sequences of the viral quasispecies. Potential changes of carbohydrate moieties were recorded in two glycosylation sites, suggesting that oligosaccharides at these sites are not necessarily advantageous for the H3N2 subtype virus currently.

Adaptation, Physiological↗

PubMed1996

Recent influenza B viruses in Europe: a phylogenetic analysis.

BACKGROUND: Influenza B virus evolution is currently in a unique situation having two cocirculating main lineages B/Yamagata/16/88 (YM/88)-like and B/Victoria/2/87 (VI/87)-like viruses. Continuation of this bifurcation would mean development towards distinct forms resembling the HA subtypes of influenza A viruses. OBJECTIVE: We wanted to examine both intraepidemic heterogeneity and recent evolution in these two lineages. The initial purpose was to determine the geographic distribution of the two sublineages of the VI/87-like viruses in Europe in 1989-1990 under circumstances of low epidemic activity. Due to the outbreaks of YM/88-like viruses since 1991, the study was extended to contain the evolution of these viruses and their genetic relationship with the vaccine strains of that time. STUDY DESIGN: The HA1 gene sequences of 33 influenza B strains isolated in ten European countries since 1989 were determined and compared with those available through databases or personal contacts. RESULTS: The two main lineages, YM/88-like and VI/87-like viruses, both continued to circulate. In both lineages, changes in the potential glycosylation sites were observed. Two sublineages of the VI/87 lineage cocirculated during the 1989-1990 season with somewhat different geographic distributions. A high degree of intraepidemic heterogeneity was observed, as well as examples of conserved nucleotide sequences. CONCLUSIONS: It is important to follow the evolution and circulation of VI/87-like viruses. Current vaccines give poor or no protection against VI/87-like viruses in immunologically unprimed children or even in primed adults (Levandowski et al., 1991, Pyhala et al., 1994). Changes in the potential glycosylation pattern in the latest virus isolates of both main lineages have occurred and it is interesting to see the significance of these changes to viral evolution.

Journal Article↗

PubMed1996

Genetic and phylogenetic clustering of enteroviruses.

Genetic and phylogenetic analysis of enteroviruses showed that in the 5'NCR enteroviruses formed three clusters: polioviruses (PVs), coxsackievirus A type 21 (CAV21), CAV24 and enterovirus type 70 (ENV70) formed one cluster; coxsackievirus B isolates (CBVs), CAV9, CAV16, ENV71, echovirus type 11 (EV11), EV12 and all partially sequenced echoviruses and swine vesicular disease virus (SVDV) belonged to another cluster and bovine enteroviruses (BEVs) formed the third cluster. In the capsid coding region five clusters were seen: PVs, CAV21 and CAV24 formed one cluster (PV-like); ENV70 formed a cluster of its own; all CBVs, CAV9, EV11, EV12 and SVDV formed the third cluster (CBV-like); CAV16, CAV2 and ENV71 belonged to the fourth cluster (CAV16-like) and BEVs formed their own cluster (BEV-like). In the 3'NCR the same clusters were seen as in the coding region suggesting a close association of the 3'NCR with viral proteins while the cellular environment may be more important in the evolution of the 5'NCR. Secondary structures were predicted in the 3'NCR, which showed two different patterns among the five clusters. A potential pseudoknot region common in all five clusters was identified. Although the BEV-like viruses formed a separate cluster in all genomic regions, in the coding region they seem to be phylogenetically related to the CAV16-like viruses.

Animals↗

PubMed1995

Evolution of the HA1 domain of human influenza A (H1N1) virus: loss of glycosylation sites and occurrence of herald and conserved strains.

Thirty-one strains of human influenza A (H1N1) viruses isolated in Europe, mostly in Finland, from 1978-1992 were compared with respect to their nucleotide sequences coding for the HA1 portion of haemagglutinin. In 1984, at least two sublineages of H1N1 subtype viruses co-circulated in Finland. The viruses isolated after 1986 formed three sequential phylogenetic clusters. Loss of glycosylation sites, on the globular head of the HA1 portion suggests that oligosaccharides at these sites are not necessarily advantageous for the human virus. Isolation of a herald strain in Finland in June 1988 raised the question as to whether the virus was able to survive in Europe throughout the non-epidemic summer period. Demonstration of highly conserved strains, found over two continents in 1988, is further evidence of the existence of infection chains whose viruses have not been subjected to random sampling or selection events.

Amino Acid Sequence↗

PubMed1994

Molecular analysis of coxsackievirus A16 reveals a new genetic group of enteroviruses.

Coxsackievirus A16 (CAV16) a member of the Enterovirus genus of Picornaviridae, is associated with hand-foot-and-mouth disease, a febrile papulovesicular rash of childhood. We have determined the complete nucleotide sequence of the genome of the prototype strain of CAV16 which consists of 7413 nucleotides plus the poly(A) tail. Alignment of the sequence with the previously studied enteroviruses showed that the genome organization is typical for a member of this virus genus. However, the predicted amino acid sequence of individual CAV16 proteins differed from those of all previously sequenced enteroviruses by 25-62%. The genomic sequence of CAV2 in the capsid and 2A polypeptide regions was also determined. It was found to differ from that of CAV16 by no more than 5-43%. The partial nucleotide sequence of enterovirus 71 in the VP1-2A region suggested that it is also closely related to CAV16. The results indicate that CAV16, CAV2, and enterovirus 71 represent a distinct genetic group of enteroviruses.

Amino Acid Sequence↗

PubMed1994

Poliovirus type 3/Saukett: antigenic and structural correlates of sequence variation in the capsid proteins.

The Saukett/USA/50 strain is the type 3 component of the inactivated poliovirus vaccine. The capsid-coding region of genomic RNA of Saukett strains from five different sources was sequenced and the sequence differences were correlated with antigenic differences measurable with poliovirus type 3-specific neutralizing monoclonal antibodies. All strains appeared to have capsid protein genes identical in size to those of the entirely sequenced type 3 poliovirus strains. The nucleotide sequence identity between the strains was 91% on the average and the strains could be divided into three groups. Amino acid differences were seen in 30 positions located throughout the capsid region both within and outside the known antigenic sites. Substitutions at the known antigenic sites explained most of the observed antigenic differences. Use of the atomic coordinates of the crystal structure model of the Sabin 3 virus and prior data based on escape mutants and peptide scanning revealed that most of the exposed substitutions located outside the known antigenic sites are spatially associated with regions found to be antigenic by either or both of these methods.

Antigenic Variation↗

PubMed1994

Early kinetics of antibody response to inactivated influenza vaccine.

The aim was to examine the rapidity of haemagglutination inhibiting (HI) antibody response induced by immunization with a current inactivated trivalent influenza vaccine. Five to six sequential serum samples collected in autumn 1992 from each of 68 vaccinees in three age groups were studied for HI antibodies to ten influenza virus strains representing vaccine and epidemic viruses. Geometric mean titres, response rates and protection rates are presented. Response rates of > 70% were overall, but not until two weeks after the vaccination. Significant two- and four-day post-vaccination antibody responses were detected only occasionally. In previously vaccinated persons, average antibody titres to some of the viruses decreased during the first days after the vaccination. In the subsequent samples, the titres remained lower than in persons who were not vaccinated against influenza in preceding years. Protection against influenza infection may be frequently developed not until two weeks after vaccination. This has relevance to prophylactic administration of amantadine and rimantadine when an influenza A outbreak is imminent and the vaccination is late.

Journal Article↗

PubMed1993

Vaccination-induced HI antibody to influenza A(H1N1) viruses in poorly primed adults under circumstances of low antigenic drift.

In Autumn 1990, trivalent split influenza virus vaccine containing A/Taiwan/1/86(H1N1) was used to immunize healthy female employees (n = 104). The 11-12 amino acid differences in the HA1 domain of virus haemagglutinin between A/Taiwan/1/86 and representative epidemic H1N1 strains in Finland in 1991 did not result in lowered haemagglutination-inhibiting (HI) antibody responses to the latter viruses. In fact, higher prevaccination, postvaccination and postepidemic antibody titres were recorded against the new field strains than against the vaccine virus; the highest being against field strains grown exclusively in MDCK cell cultures. This pattern is primarily explained by differences in the sensitivity of the viruses for detecting HI antibodies. Postvaccination protection rates of 98-100% for the MDCK-grown avid viruses were noted in subjects who exhibited prevaccination antibody. Lower protection rates were recorded in initially seronegative subjects, the lowest (54-57%) being among older people, i.e. among vaccines born in 1930-1955 (p < 0.001). Moreover, conspicuous decreases in protection rates were detected during the following epidemic season in the initially seronegative subjects. Diagnostic findings during outbreaks due to H1N1 subtype viruses also support the impression that many middle-aged people are poorly primed. Thus, vaccination with two doses may be worth considering when such people join the high-risk group and receive influenza vaccine for the first time.

Adult↗

PubMed1992

A distinct picornavirus group identified by sequence analysis.

Although echovirus 22 is presently classified as a member of the enterovirus group in the family of picornaviruses, it has been reported to have exceptional biological properties when compared with other representatives of the group. We have determined the complete nucleotide sequence of the echovirus 22 (Harris strain) genome, which appears to be significantly different from all the other studied picornaviruses. However, the organization of the genome [7339 nucleotides, excluding the poly(A) tract] is similar to that of previously sequenced picornaviruses. This genome includes a 5' untranslated region, relatively well-conserved when compared with aphtho- and cardioviruses, followed by an open reading frame coding for a 2180-amino acid-long polyprotein. The amino termini of capsid polypeptides VP1 and VP3 were determined by direct sequencing, and the other proteolytic cleavage sites in the polyprotein were predicted by comparison with other picornavirus proteins. The amino acid identities of echovirus 22 polypeptides with the corresponding proteins of other picornaviruses are in the 14-35% range, similar to those percentages seen when representatives of the five picornavirus groups (entero-, rhino-, cardio-, aphtho-, and hepatoviruses) are compared. Our results suggest that echovirus 22 belongs to an independent group of picornaviruses.

Amino Acid Sequence↗