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M P Koopmans

Publications and source records attributed to M P Koopmans.

At least 19 recordsLinked to original sources

Genetic polymorphism across regions of the three open reading frames of "Norwalk-like viruses".

Genomic characterization of Norwalk-like human caliciviruses (NLVs) originating from outbreaks and sporadic cases of acute gastroenteritis has revealed surprisingly high levels of diversity, even in the RNA polymerase gene, which is anticipated to be highly conserved. Since information on antigenic relationship is limited, due to the lack of a tissue culture system for these viruses, strains mostly are described on the basis of their genetic relatedness. However, the lack of uniformly applied criteria has led to a confusing array of strains with different groups employing different names for similar genetic lineages. Our goal was to conduct a structured analysis of genomic relationships among NLV strains in an attempt to provide an interim framework for genotyping. We assembled a panel of 31 potentially distinct genogroup I (GGI) and genogroup II (GGII) NLVs that reflected the diversity seen in strains detected by our laboratories and in published sequences. Phylogenetic analysis of sequences from regions of the open reading frames (ORF) 1, 2 and 3 was performed in order to investigate genomic relationships. The strains sequenced fell into seven phylogenetic groups in GGI and at least five phylogenetic groups in GGII, based on greater than 80% nucleotide identity in the region of ORF2 encoding the N-terminus of the capsid protein, and consistent clustering with high bootstrap values irrespective of the method used. Analysis of the ORF1 and ORF3 regions supported for most strains the clustering as established for those derived from ORF2. In the ORF1 region, used by most laboratories for diagnostic RT-PCR, clustering was consistent when a putative genotype border was set at 15% nucleotide mismatches for viruses in GGI and at 10% for viruses in GGII. Two strains grouped within different clusters based on ORF1 and ORF2 indicating that recombination may have occurred. We discuss the implications of these observations for the classification and typing of NLVs.

Caliciviridae↗

Mucosal and systemic immunity against poliovirus in mice transgenic for the poliovirus receptor: the poliovirus receptor is necessary for a virus-specific mucosal IgA response.

In view of the planned eradication of poliovirus, the suitability of transgenic mice bearing the human receptor for poliovirus (PVRtg mice) as a nonprimate animal model to study mucosal immunity against poliovirus was investigated. After intraperitoneal (ip) priming followed by ip or oral booster with live poliovirus, PVRtg mice had detectable IgA and IgG responses. The IgA response was restricted to PVRtg mice and could not be induced by oral immunization. After ip priming, PVRtg mice did shed virus in the stool, whereas control mice did not. Moreover, the amount of virus shed in the stools of PVRtg mice that had an IgA response after immunization was significantly lower than that of nonimmunized mice. A virus-specific mucosal IgA response is dependent on expression of the poliovirus receptor and is influenced by the route of immunization and the virus strain. PVRtg mice are a suitable model for the study of poliovirus-specific immunity and protection against poliovirus infection.

Animals↗

Antibody responses to antigenic sites 1 and 3 of serotype 3 poliovirus after vaccination with oral live attenuated or inactivated poliovirus vaccine and after natural exposure.

Three important antigenic sites involved in virus neutralization on polioviruses in mouse experiments have been identified. These sites are located at the surface of the virion and have been designated antigenic sites 1, 2, and 3. In mice, the antibody response to antigenic site 1 of serotype 3 poliovirus is considered to be immunodominant, but little is known about the immunogenicity of these sites in humans. In the present study, we developed inhibition enzyme-linked immunosorbent assays specific for antigenic sites 1 and 3 to measure antibody responses to these sites in fully vaccinated inactivated poliovirus vaccine (IPV) (n = 63) and oral live attenuated poliovirus vaccine (OPV) (n = 63) recipients and in naturally infected persons (n = 25). Similar levels of antibodies to site 1 in IPV and OPV vaccinees were detected. However, significantly more OPV recipients (88.7%) had detectable antibodies to antigenic site 3 (P < 0.01) than did IPV-vaccinated persons (63. 1%). After an IPV booster vaccination, both previously IPV- and OPV-vaccinated persons responded with a significant increase in antibodies to sites 1 and 3 (P < 0.01). We conclude that the immune response to serotype 3 poliovirus in humans consists of both site 1- and site 3-specific antibodies and that these responses can be induced by either OPV or recent IPV vaccination.

Antibodies, Monoclonal↗

Molecular detection and epidemiology of Sapporo-like viruses.

Sapporo-like viruses (SLVs) are associated with acute gastroenteritis in humans. Due to a limited supply of available reagents for diagnosis, little is known about the incidence and pathogenicity of these viruses. We have developed a first-generation generic reverse transcriptase (RT) PCR assay based on a single primer pair targeting the RNA polymerase gene. With this assay, 55 (93%) of the 59 stool specimens collected in a 10-year period of time (1988 to 1998) and containing typical caliciviruses by electron microscopy tested positive and could be confirmed by Southern hybridization. By phylogenetic analysis, most SLV strains could be classified into one of the three recently described genotypes. However, three samples clustered separately, forming a potential new genotype. We sequenced the complete capsid gene of one of the strains in this cluster: Hu/SLV/Stockholm/97/SE. Alignment of the capsid sequences showed 40 to 74% amino acid identity among strains of the different clusters. Phylogenetic analysis of the aligned sequences confirmed the placing of Hu/SLV/Stockholm/97/SE into a new distinct genetic cluster. This is the first report on the development of a broadly reactive RT-PCR assay for the detection of SLVs.

Adult↗

Simultaneous detection and genotyping of "Norwalk-like viruses" by oligonucleotide array in a reverse line blot hybridization format.

"Norwalk-like viruses" (NLVs) are the most common cause of outbreaks of nonbacterial gastroenteritis worldwide. To date, the method most widely used for typing of NLV strains is sequencing and subsequent phylogenetic analysis of reverse transcription (RT)-PCR products, which has revealed the existence of stable distinct lineages (genotypes). This typing method is rather costly, not routinely used in clinical laboratories, and not very suitable for the analysis of large numbers of samples. Therefore, we have developed a rapid and simple method for genotyping of NLVs. The method, designated reverse line blot hybridization, is based on the nucleotide divergence of a region of the gene for RNA polymerase which can be used to classify NLVs into genotypes. NLV RNA was amplified by RT-PCR and then hybridized to 18 different membrane-bound oligonucleotides that were able to discriminate among 13 NLV genotypes. Application of the method to a panel of 132 positive stool samples from 34 outbreaks and 20 sporadic cases of gastroenteritis collected in a 6-year period (1994 to 1999) resulted in successful genotyping of 124 samples (94%), as confirmed by phylogenetic analysis. The nucleotide sequences of the remaning eight strains (6%) from three outbreaks did not cluster with the known NLV genotypes. Phylogenetic analysis of the complete and partial open reading frame 2 (capsid gene) sequences of these strains revealed the existence of one novel genotype (Alphatron) and one potentially novel genotype (Amsterdam). This novel method, which allows simultaneous detection and genotyping of NLVs, is useful in the diagnosis and typing of NLVs obtained from outbreaks and in large-scale epidemiological studies.

Caliciviridae Infections↗

Induction of mucosal immunity by inactivated poliovirus vaccine is dependent on previous mucosal contact with live virus.

The inactivated poliovirus vaccine (IPV) is used for protection against poliomyelitis in The Netherlands. It is not clear, however, whether IPV vaccination can lead to priming of the mucosal immune system and the induction of IgA. It has been demonstrated that IPV vaccination is able to induce strong memory IgA responses in the serum of persons who have been naturally exposed to wild-type poliovirus. This has led to the hypothesis that IPV vaccination is able to induce poliovirus-specific IgA at mucosal sites in persons who have been previously primed with live poliovirus at mucosal sites. To test this hypothesis, the kinetics of the IgA response in serum and saliva after IPV vaccination were examined in persons previously vaccinated with oral poliovirus vaccine (OPV) or IPV. ELISA and enzyme-linked immunospot assays were used for the detection of poliovirus-specific IgA responses. In addition, B cell populations were separated on the basis of the expression of mucosal (alpha4beta7 integrin) and peripheral homing receptors (L-selectin). Parenteral IPV vaccination was able to boost systemic and mucosal IgA responses in previously OPV-vaccinated persons only. None of the previously vaccinated IPV recipients responded with the production of IgA in saliva. In agreement with this finding, a large percentage of the poliovirus-specific IgA-producing lymphocytes detected in previous OPV recipients expressed the alpha4beta7 integrin. It is concluded that IPV vaccination alone is insufficient to induce a mucosal IgA response against poliovirus. In mucosally (OPV-) primed individuals, however, booster vaccination with IPV leads to a strong mucosal IgA response.

Adult↗

Lessons from diagnostic investigations of patients with poliomyelitis and their direct contacts for the present surveillance of acute flaccid paralysis.

One of the key strategies for the global eradication of poliomyelitis is the virological investigation of stool samples in cases of acute flaccid paralysis (AFP) to exclude poliovirus as a possible cause. Clinical specimens from a serotype 3 outbreak provided an opportunity to examine the potential of newly developed methods for the diagnosis of poliomyelitis. The virus isolation rate was maximal (89.6%) during the first 2 weeks after the onset of paralysis and then dropped sharply to 18.6%. In contrast, a high percentage of patients tested positive for poliovirus-specific IgM (93.9%) in the early phase of the infection and remained positive for up to 8 weeks. Virus isolation would have correctly identified only 54.9% of the AFP cases. This rate would have been increased to 92% through the use of the poliovirus-specific IgM ELISA. The IgM ELISA could serve as an important additional tool for the rapid diagnosis of poliomyelitis.

Acute Disease↗

A Sabin vaccine-derived field isolate of poliovirus type 1 displaying aberrant phenotypic and genetic features, including a deletion in antigenic site 1.

Poliovirus strains derived from the oral poliovirus vaccine (Sabin) can be differentiated from wild-type poliovirus by tests based on either immunological or genetic properties of the strains. The characterization of a recently identified poliovirus type 1 isolate with exceptional properties is described. Initial phenotypic analysis of the virus by use of polyclonal absorbed antisera suggested a wild-type character. However, the different genomic analyses all confirmed the Sabin-derived character of the virus. All 17 plaques isolated from the strain shared these properties, thus excluding the possibility of a mixture of a wild-type and a Sabin-derived strain. To elucidate the properties of this virus further, the nucleotide sequences of the P1 region and most of the 5' non-coding region were established. Although the nucleotide identity with Sabin 1 was more than 99.4%, mutations were observed in regions encoding three major antigenic sites; the deduced amino acid substitutions confirmed the aberrant results of micro-neutralization assays with site-specific monoclonal antibodies. The most striking feature was the existence of a hexanucleotide deletion in the VP1 gene, which gave rise to a two amino acid deletion in the BC loop. In spite of these antigenic changes, the strain was readily serotyped as poliovirus type 1 under standard conditions. Likewise, replication of the virus under cell culture conditions was not affected by these mutations or by the deletion. Standard polio vaccination protects against this aberrant virus, and its epidemiological significance remains open.

Amino Acid Sequence↗

Molecular detection of Norwalk-like caliciviruses in sewage.

In this study, Norwalk-like virus (NLV) RNA was detected by reverse transcriptase PCR (RT-PCR) in sewage water concentrates. Sequence analysis of the RT-PCR products revealed identical sequences in stools of patients and related sewage samples. In 6 of 11 outbreak-unrelated follow-up samples, multiple NLV genotypes were present. Levels as high as 10(7) RNA-containing particles per liter were found. These data show that high loads of NLVs may be present in sewage and warrant further studies addressing the efficacy of NLV removal by sewage water treatment processes.

Caliciviridae Infections↗

Genetic basis for immunological aberrations in poliovirus Sabin serotype 3 strains imported in the netherlands.

During the characterization of poliovirus type 3 strains imported in The Netherlands, Sabin serotype 3 strains that reacted with both specific antisera against Sabin-like (vaccine) and non-Sabin-like (wild-type) strains by the intratypic strain differentiation assay have been found. The present study was done to determine the pathogenic potential of these virus strains for humans. Characterization of these so-called double-reactive strains with neutralizing monoclonal antibodies (MAbs) against the major antigenic sites of serotype 3 Sabin virus led to the identification of two groups with different antigenic properties. Six of the seven strains were resistant to neutralization with MAbs against sites 2B and 3B and one strain was neutralized by all the MAbs in a manner similar to that for the Sabin serotype 3 virus. Partial sequencing of the coding regions confirmed the antigenic changes for all six antigenically distinct strains. By inoculation of these viruses into transgenic mice which express the human poliovirus receptor, one strain was identified as highly neurovirulent, three were identified as intermediate, and three were identified as attenuated. Sera from vaccinated persons efficiently neutralized the mutants. Our data suggest that some double-reactive strains are a potential risk to the unvaccinated community but not to the vaccinated population.

Animals↗

Age-stratified seroprevalence of neutralizing antibodies to astrovirus types 1 to 7 in humans in The Netherlands.

Astroviruses are a new family of positive-stranded RNA viruses that cause gastroenteritis in a wide range of animals and in humans. Seven types of astrovirus, tentatively considered serotypes, have been distinguished by enzyme-linked immunosorbent assays (ELISA) or immunoelectron microscopy, but it is unclear whether the serotype designation is used properly. To test human sera for the presence of neutralizing antibodies and to type field strains, neutralization tests (NT) using CaCo2 tissue-culture-adapted astrovirus strains 1 to 7 and the corresponding rabbit reference sera were developed. In rabbits, neutralizing antibodies were predominantly serotype specific, with the exception of low-level cross-reactivity in astrovirus serotype 4 reference serum with astrovirus serotype 1 virus. Similarly, in humans, no evidence of cross-reactivity was found for the serotype combinations tested (all except the combination 1 and 7 and the combination 6 and 7). Typing by NT was concordant with typing by ELISA and genotyping, with one exception. The seroprevalence rates of neutralizing antibodies in an age-stratified sample of the population in Utrecht Province (n = 242) were 91% for astrovirus serotype 1, 69% for astrovirus serotype 3, 56% for astrovirus serotype 4, 36% for astrovirus serotype 5, 31% for astrovirus serotype 2, 16% for astrovirus serotype 6, and 10% for astrovirus serotype 7. Acquisition of antibodies was slower among persons seropositive for astrovirus serotype 5 than among those seropositive for astrovirus serotypes 1 to 4, suggesting that the epidemiology of serotype 5 astrovirus is different from that of astrovirus serotypes 1 to 4.

Adolescent↗

Genetic analysis of wild-type poliovirus importation into The Netherlands (1979-1995).

Wild polioviruses were isolated a number of times in The Netherlands outside the epidemic periods (1978 and 1992-1993) from patients infected abroad, from subclinically infected persons, and from river water. Sequence comparisons revealed discrete sources of importation: the Mediterranean, India, and Indonesia. The observed wide genetic variation is indicative of repeated importation and not of indigenous circulation. Isolates identical or closely related to the epidemic type 1 strain of 1978 were found in clinical and environmental specimens until 1983, probably due to repeated importation from Turkey. Viruses related to the 1992-1993 epidemic type 3 virus had already been isolated six times before the epidemic. Of particular importance are two documented isolations of prototype wild poliovirus indistinguishable from that used to produce the inactivated vaccine. These data underscore the continued risk to the unvaccinated religious population of exposure to wild poliovirus.

Adoption↗

The incidence and genetic variability of small round-structured viruses in outbreaks of gastroenteritis in The Netherlands.

Small round-structured viruses (SRSV) are a group of RNA viruses that can cause gastroenteritis in persons of all ages. To determine the incidence of SRSV-associated gastroenteritis in The Netherlands and to study the genetic variability of outbreak strains, all outbreaks that were reported to the epidemiologists of the regional health services in 1996 were investigated using a standardized protocol. In 60 (87%) of the 69 reported outbreaks, SRSV could be detected, showing the etiologic significance of SRSV in outbreaks of gastroenteritis in The Netherlands. Of these outbreaks, 84% occurred in semiclosed communities, such as nursing homes (59%) and hospital wards (25%). Sequence analysis of the outbreak strains revealed that the majority of the strains from January to November 1996 formed a tight cluster within genogroup II SRSV. In November 1996, a shift toward genogroup I SRSV occurred, suggesting a change to a new predominant strain.

Age Factors↗

Association of torovirus with acute and persistent diarrhea in children.

OBJECTIVE: To study the etiologic role of toroviruses as a cause of gastroenteritis in humans. METHODS: The design was a case-control study. We compared the rate of torovirus detection in fecal specimens from a selection of children with acute or persistent diarrhea and controls without diarrhea from a study of childhood diarrhea in an urban Brazilian slum. Stool samples were coded and tested in a blinded fashion for the presence of torovirus antigen by enzyme-linked immunosorbent assay, other enteropathogens, toxins and fecal leukocytes. RESULTS: Thirty-three children with acute diarrhea, 41 children with persistent diarrhea and 17 controls were enlisted in the study. Torovirus antigen was detected in 9 (27%) samples from children with acute diarrhea, 11 (27%) samples from children with persistent diarrhea and none of the samples from controls (P < 0.05). In addition the presence of enteroaggregative E. coli was associated with persistent diarrhea and the presence of Cryptosporidium oocysts was common although not significant (P = 0.08); torovirus and Cryptosporidium occurred in different subsets of samples, whereas torovirus and enteroaggregative Escherichia coli were commonly found in combination. CONCLUSIONS: These data indicate that toroviruses, alone or in combination with enteroaggregative E. coli, may play a pathogenic role in acute and possibly persistent diarrhea. Further studies are warranted to determine the etiologic role of toroviruses in gastroenteritis.

Acute Disease↗

Poliovirus-specific immunoglobulin A in persons vaccinated with inactivated poliovirus vaccine in The Netherlands.

In The Netherlands the inactivated poliovirus vaccine (IPV) is used for protection against poliomyelitis. It is not clear if parenteral vaccination with IPV can lead to priming of the mucosal immune system. We developed and evaluated enzyme-linked immunosorbent assays for the detection of poliovirus serotype-specific immunoglobulin A (IgA) and secretory IgA antibodies. Using these assays we examined the kinetics of the IgA response in sequential serum samples from 15 poliomyelitis patients after natural infection with serotype 3 poliovirus. In 36% of the patients IgA remained present for up to 5 months postinfection. Furthermore, we examined, in an IPV-vaccinated population, the presence of IgA antibodies in sera from young children (4 to 12 years of age; n = 177), sera from older children (between 13 and 15 years of age; n = 123), sera from healthy blood donors (n = 66), and sera from naturally immune elderly persons (n = 54). The seroprevalence of IgA to all three serotypes was low in young vaccinated children (5 to 7%), and the seroprevalence of IgA types 2 and 3 was low in older vaccinated children (2 to 3%). The seroprevalence of antibodies to type 1 was significantly higher (18%) in older children than in younger children. This higher seroprevalence is most likely explained by the persistence of IgA following infection with the serotype 1 wild-type poliovirus strain during the 1978 epidemic. In healthy adults, the seroprevalence of type 1- and type 2-specific IgA was significantly higher than that in young children. These results suggest that at least part of the IgA found in the older population is induced by infections unrelated to the IPV vaccination schedule. Finally, we found that parenteral vaccination with IPV was able to boost secretory IgA responses in 74 to 87% of a naturally exposed elderly population (n = 54). While the presence of secretory IgA in IPV-vaccinated persons has been documented previously, our findings suggest that mucosal priming with live virus is necessary to obtain an IgA response after IPV booster vaccination.

Adolescent↗

Evaluation of a poliovirus-binding inhibition assay as an alternative to the virus neutralization test.

An enzyme-linked immunosorbent assay (ELISA)-based poliovirus-binding inhibition (PoBI) test to detect and quantify antibodies to polioviruses was optimized and evaluated for use in population studies as an alternative to the virus neutralization test (NT) in tissue culture. The sensitivities of the inhibition ELISA compared with the NT in an inactivated poliovirus vaccine (IPV)-vaccinated population were 98.6, 97.4, and 92.1% for serotypes 1, 2, and 3, respectively. The specificities of the PoBI test, as determined with sera from nonvaccinated persons, were also high for all three serotypes (99.0, 95.8, and 100%, respectively). Antibodies to other enteroviruses did not cross-react in the serotype 1 and 3 PoBI, and only levels of cross-reactivity were found for serotype 2. We found high correlations between the PoBI and NT titers for serotypes 1 and 2 in IPV-vaccinated blood donors (0.97 and 0.95), in oral poliovirus vaccine (OPV)-vaccinated blood donors (0.91 and 0.95), and in naturally immune persons (0.90 and 0.87). The correlation coefficient for serotype 3, however, was significantly lower in OPV-vaccinated blood donors (0.73) and in naturally immune persons (0.76) than in IPV-vaccinated persons (0.94; P < 0.01). These results indicate that the antibody response to serotype 3 poliovirus in IPV recipients is different from that in OPV recipients and naturally infected persons. We conclude that the PoBI test is a suitable alternative to the NT for estimating the seroprevalence of neutralizing antibodies to poliovirus, especially in large-scale population studies.

Animals↗