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Biomedical subjects

D O Matson

Publications and source records attributed to D O Matson.

At least 19 recordsLinked to original sources

Role of human-milk lactadherin in protection against symptomatic rotavirus infection.

BACKGROUND: Human milk contains a 46 kDa mucin-associated glycoprotein, lactadherin, which binds specifically to rotavirus and inhibits its replication. This study tested the hypothesis that lactadherin protects against symptoms of rotavirus infection. METHODS: 200 infants in Mexico City were recruited at birth and monitored by regular stool EIA for rotavirus, serology, and recording of feeding and stool patterns. Milk samples were obtained from the mothers weekly until 4 weeks post partum then monthly. The sample taken immediately before an infant's episode of rotavirus infection was assayed for lactadherin, butyrophilin, mucin, and secretory IgA. An infection was defined as symptomatic if diarrhoea occurred in the 5 days before or after detection of the virus. FINDINGS: 31 infants developed rotavirus infection; 15 were symptomatic and 16 had no symptoms. The median concentration of lactadherin in the milk samples (obtained 4-41 days [median 13] before the infection) was 48.4 (range 5.6-180) microg/mL in the asymptomatic group and 29-2 (6.2-103-4) microg/mL in the symptomatic group. Although these medians did not differ significantly, in logistic regression analysis adjusted for age at infection and secretory IgA concentration there was a significant difference between the groups (p=0O01). No association between symptom status and concentrations of butyrophilin, mucin, or secretory IgA was found. INTERPRETATION: Protection against rotavirus by human milk is associated with the glycoprotein lactadherin. This association is independent of products of the secretory immune system.

Adult

Genomic mapping of a calicivirus VPg.

We identified a primate calicivirus (Pan-1) VPg in Pan-1-infected cells. The Pan-1 VPg was associated with both genomic and subgenomic RNAs. RNase digestion of Pan-1 RNA yielded a residual protein of 16 kDa. The N-terminal sequence of Pan-1 VPg was determined by direct amino acid sequencing and mapped to a region of the genome equivalent to picornavirus VPgs. Alignment of this protein sequence with similar regions of other calicivirus genomes allowed identification of conserved amino acid motifs and potential boundaries of the calicivirus VPg genes. Proteinase K treatment abolished the infectivity of Pan-1 RNA, suggesting that Pan-1 VPg is required for RNA infectivity.

Amino Acid Sequence

Seroprevalence of Norwalk virus and Mexico virus in Chilean individuals: assessment of independent risk factors for antibody acquisition.

Norwalk virus (NV) and Mexico (MX) virus represent distinct genetic clusters within the same genus of human caliciviruses (CVs), a major cause of diarrhea in adults. The magnitude and potential risk factors of human CV infection in populations from Santiago and Punta Arenas, Chile, were assessed. Individuals (n = 1,864) gave a blood sample and answered a questionnaire during a household survey. Sera were tested for antibody to NV and MX virus with use of recombinant capsid antigens. Overall, NV and MX virus seroprevalence rates were 83% and 91% in Santiago vs. 67% and 90% in Punta Arenas, respectively (P < .001 for NV virus). Lower socioeconomic status and increasing age were risk factors for infection with both viruses (P < .001). Consumption of seafood, consumption of vegetables, and child care center attendance were population risk factors for infection, but the association of a factor with a virus depended on the city. Prevention of human CV infections will require individual assessment in different communities.

Adolescent

Pathogen transmission in child care settings studied by using a cauliflower virus DNA as a surrogate marker.

Two regions of cauliflower mosaic virus DNA were designed as markers to study pathogen transmission in a child care home (CCH) and child care center (CCC) and in homes of CCC children. The DNA markers were stable for 1 month in the environment. The DNA markers were introduced into the environment through sensitized objects, and spread in the environment was traced by detection of the markers with polymerase chain reaction. The DNA markers spread rapidly in both the CCH and CCC after introduction and spread more rapidly in the toddler room than in the infant room of the CCC. Hand touching of contaminated areas was the major factor leading to spread of the markers. Hand washing and surface wiping decreased spread of the markers. The markers spread minimally from room to room in the CCC but were detected in the children's homes after introduction of markers in the CCC.

Adult

In vitro isolation and characterization of a calicivirus causing a vesicular disease of the hands and feet.

We report that a calicivirus of oceanic origin, San Miguel sea lion virus serotype 5 (SMSV-5), is a human pathogen. This biotype was isolated originally from blisters on the flippers of northern fur seals (Callorhinus ursinus) and replicates readily in primate and human cell lines. It infects a phylogenetically diverse array of hosts (poikilotherms to primates) and induces type-specific neutralizing antibodies in exposed humans. Group antibody against a pooled antigen of SMSV-5 and two other serotypes was also observed in 18% of 300 blood donors from a population in the northwestern United States. The human calicivirus isolate designated SMSV-5 Homosapien-1 (SMSV-5 Hom-1) was recovered from a laboratory worker with systemic illness, including vesicular lesions on all four extremities. We believe this newly described human disease represents a paradigmatic shift in calicivirus disease recognition.

Adult

Isolation of reptilian calicivirus Crotalus type 1 from feral pinnipeds.

Ten virus isolates were obtained from three species of marine mammals sampled on San Miguel Island (California, USA) and 1,200 km north on Rogue Reef (Oregon, USA) during tagging operations in 1986-87. Seven of these 10 were derived from 30 sampled Steller sea lion (Eumetopias jubatus pups, while two of 10 were isolated from one of 19 sampled California sea lion (Zalophus californianus californianus pups, and the remaining isolate was derived from 30 sampled northern fur seal (Callorhinus ursinus) pups. All 10 isolates were identified as belonging to a single serotype, reptilian calicivirus Crotalus type 1 (RCV Cro-1), previously isolated from both healthy and diseased snakes and frogs in a California zoologic collection. The marine samples also showed that nine of 30 Steller sea lion pups, one of 19 California sea lion pups and zero of 30 fur seal pups were producing type specific neutralizing antibodies to RCV Cro-1. This represents the first reported instance of the isolation from marine sources of calicivirus originally isolated from a terrestrial species.

Animals

Phylogenetic analysis of the Caliciviruses.

A phylogenetic portrait of the genus Calicivirus in the family Caliciviridae was developed based upon published sequences and newly characterized calicivirus (CV) strains, including additional Sapporo-like HuCV strains in pediatric diarrhea stool specimens from South Africa, the United Kingdom, and the United States. Distance and parsimony methods were applied to nucleotide and amino acid sequences of human and animal calicivirus 3D RNA-dependent RNA polymerase (approximately 470nt) and capsid hypervariable regions (approximately 1,200nt) to generate phylogenetic trees. Pairwise amino acid identity in the 3D region among the Sapporo-like strains ranged from 61% to 100%. Human and animal caliciviruses (HuCVs and AnCVs) separated into five genogroups: small round-structured viruses (SRSV), Sapporo-like, and hepatitis E virus (HEV)-like HuCVs and rabbit-, and vesicular exanthema of swine virus (VESV)-like AnCVs, each with a distinct genome organization. Each genogroup, including the Sapporo-like HuCVs, subdivided further into subgenogroups. The capsid region trees had higher levels of confidence than the 3D region trees and limited conclusions about genogroups could be drawn from the 3D region analyses. This analysis suggested that CVs include five potential virus subfamilies.

Amino Acid Sequence

Sapporo-like human caliciviruses are genetically and antigenically diverse.

The Sapporo-like human caliciviruses (HuCVs) comprise one of three genogroups of HuCVs associated with acute gastroenteritis. Phylogenetic analysis has shown that Sapporo-like HuCVs are related more closely to animal caliciviruses than to other known HuCVs. We produced 3.2 kb cDNA fragments from the 3' end to three Sapporo-like HuCVs that were associated with acute gastroenteritis in children (Houston/86, Houston/90, and London/92). Sequence analysis of the 3.2 kb cDNAs showed that two of the three viruses had a genomic organization similar to that of other Sapporo-like strains and the third strain (London/92) lacked an open reading frame overlapping the 5' end of the capsid gene. Alignment of the capsid sequences of these three strains showed 44-78% amino acid identity among the three strains. Phylogenetic analysis of the aligned sequences indicated the three strains are related but each belongs to a distinct genetic cluster. The genetic differences are associated with antigenic differences in that an enzyme immune assay (EIA) specific for the prototype Sapporo/82 strain detected the Houston/86 strain, but not the Houston/90 and London/92 strains. In vitro transcription and translation of viral cDNA containing the predicted capsid gene of Houston/90 resulted in a protein of 63 K, which is immunoprecipitated by sera from children infected with the strain. Genetically and antigenically distinct strains in the Sapporo-like HuCVs have not been described previously and the occurrence of such diverse strains in the same community likely increases the importance of these strains as a cause of illness in children.

Amino Acid Sequence

Molecular epidemiology of human rotaviruses in Santiago, Chile.

BACKGROUND: Protective immunity against rotavirus infection is directed against antigenic epitopes on the outer capsid proteins VP7 and VP4. Our aim was to characterize the epidemiology of rotavirus antigenic types over time in Santiago, Chile. METHODS: We prospectively obtained 2097 stool samples for rotavirus testing, VP7 (G1 to G4) and VP4 (P4, P6, P8, P9) typing from children with diarrhea evaluated in emergency rooms of 5 base hospitals of Santiago. In addition 256 rotavirus-positive samples collected between 1985 and 1987 in the north health care area of Santiago were studied. RESULTS: Of 995 rotavirus-positive samples obtained 825 (82%) were typable for 1 or more VP7 types. G1 represented 81% of the G-typed samples during 1993 through 1995 and 77% during 1985 through 1987, predominating in all health care areas. G2 was next most common in all 5 areas, representing 6 to 23% of typed samples, with 1 area, the Southeast concentrating a significantly higher number of G2 infections. G2 declined from 35% of rotavirus-positive samples in 1993 to 0% in 1995 (P < 0.001), and from 25% to 2% in the north health care area from 1985 to 1987 (P < 0.001). G4 was uncommon and significantly more prevalent in 1985 through 1987 than in 1993 through 1995 (7% vs. 3%, P = 0.015). G3 was not detected. G1P8 (53%) and G2P4 (16%) combinations were by far the most commonly detected G-P associations. CONCLUSIONS: In Santiago, Chile, rotavirus antigenic type G1P8 has been highly prevalent and G2P4 has circulated in cycles. Differences in epidemiology of rotavirus antigenic types worldwide may prove to be relevant in efficacy of rotavirus vaccines.

Child

Rotavirus infection in infants as protection against subsequent infections.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea in infants. To provide a base line for assessing the efficacy of rotavirus vaccines, we evaluated the protection that is conferred by natural rotavirus infection. METHODS: We monitored 200 Mexican infants from birth to two years of age by weekly home visits and stool collections. A physician assessed the severity of any episodes of diarrhea and collected additional stool specimens for testing by enzyme immunoassay and typing of strains. Serum collected during the first week of life and every four months thereafter was tested for antirotavirus IgA and IgG. RESULTS: A total of 316 rotavirus infections were detected on the basis of the fecal excretion of virus (56 percent) or a serologic response (77 percent), of which 52 percent were first and 48 percent repeated infections. Children with one, two, or three previous infections had progressively lower risks of both subsequent rotavirus infection (adjusted relative risk, 0.62, 0.40, and 0.34, respectively) and diarrhea (adjusted relative risk, 0.23, 0.17, and 0.08) than children who had no previous infections. No child had moderate-to-severe diarrhea after two infections, whether symptomatic or asymptomatic. Subsequent infections were significantly less severe than first infections (P=0.024), and second infections were more likely to be caused by another G type (P=0.054). CONCLUSION: In infants, natural rotavirus infection confers protection against subsequent infection. This protection increases with each new infection and reduces the severity of the diarrhea.

Antibodies, Bacterial

Outbreaks of gastroenteritis in elderly nursing homes and retirement facilities associated with human caliciviruses.

Eleven outbreaks of acute gastroenteritis, eight of which were in nursing homes or retirement facilities, were reported in virginia during the winter of 1993-1994. Serum samples (four outbreaks) and stool samples (two outbreaks) from involved people were tested for human calicivirus (HuCV) infection by enzyme immune assays (EIAs) using recombinant Norwalk virus (rNV) and Mexico virus (rMX) capsid antigens and reverse transcription-polymerase chain reaction (RT-PCR). Of the 31 pairs of acute and convalescent serum specimens tested, 24 had a fourfold or more titer increase to rMX and 4 responded to rNV. In all four outbreaks, the geometric mean titers (GMTs) against rMX were significantly higher than those against rNV in the convalescent, but not in the acute phase of illness. The antibody response to rMX among these patients was also higher than to rNV (summary mean 32-fold increase vs. 0.7-fold increase, respectively, P < .001). Antigen was detected in 5 of 21 stool specimens tested by the rMX EIA, RNA in 12 of 17 stool specimens tested by RT-PCR, and small round structured virus (SRSV) particles in 12 of 21 by electron microscopy (EM); none were positive by the rNV EIA. Sequence analysis of the RT-PCR-amplified products from the viral RNA polymerase region revealed 92-93% amino acid identity with Snow Mountain agent (SMA), 86% with MX, 58-59% with NV, and 31-32% with Sapporo HuCV, suggesting that these viruses belong to the SMA HuCV genogroup.

Aged

Protective immunity against group A rotavirus infection and illness in infants.

Understanding of the protective effect provided by natural rotavirus infections against subsequent rotavirus infections is required for evaluating vaccine development programs. Prior studies of the protective efficacy of natural infections and correlates of natural protection are reviewed and results from several studies presented only in abstract form are summarized to provide a current assessment of knowledge in this area. Six cohort studies have reported rates for the protective efficacy of a natural rotavirus infection against subsequent infection, diarrhea, or severe diarrhea. These efficacy estimates ranged from 0 to 100% and are not directly comparable because of differences in methodology and population monitored. Results from other study designs also have been confusing, until recently. Recent studies have identified immunologic correlates of protection and studies from a cohort of intensely monitored Mexican children promise to provide a comprehensive assessment of the strength of the protective effect of natural rotavirus infection.

Animals

Genetic and antigenic diversity of human caliciviruses (HuCVs) using RT-PCR and new EIAs.

RT-PCR using primers from conserved regions of calicivirus genomes, followed by sequencing, permits characterization of genetic variation within the family. EIAs based on baculovirus-expressed viral capsid proteins and hyperimmune antisera against the capsid proteins were developed to detect HuCV antigens and antibodies. Serologic surveys using recombinant Norwalk virus (rNV) and recombinant Mexico virus (rMX, a SMA-like virus) EIAs showed that infections by HuCVs are common and that children acquire antibodies to HuCVs at an early age in both developed and developing countries. Three HuCV genogroups have been described that are represented by Norwalk virus (NV), Snow Mountain agent (SMA), and Sapporo virus, although recently accumulated sequences of HuCV strains indicate these genogroups can be further divided. These genogroups also correspond to distinct antigenic groups based on the results of the recombinant EIAs. The three genogroups co-circulate and have a worldwide distribution, although the SMA genogroup seems to be predominant currently. Application of these new assays for further characterization of the genetic and antigenic properties of HuCVs remains an important task for HuCV research.

Antibodies, Viral

The epidemiology of human calicivirus/Sapporo/82/Japan.

Based on genome analysis of the RNA-dependent RNA polymerase region, it has been proposed that human caliciviruses (HuCV) can be classified into at least three genogroups: genogroup I is represented by Norwalk virus (NV), genogroup II by Snow Mountain agent (SMA) and genogroup III by HuCV/Sapporo/82/Japan (HuCV/Sa/82/J) virus. HuCV/Sa/82/J strain is genetically unique and more closely related to animal caliciviruses than are other known HuCVs, such as NV and SMA. HuCV/Sa/82/J strain was detected in four outbreaks of HuCV gastroenteritis occurring between 1977 and 1982 in an infant home in Sapporo. The HuCVs detected from these four outbreaks all showed a typical "Star of David" configuration by electron microscopy (EM), and they were identical antigenically and genetically. This strain has also been detected in other prefectures in Japan, as well as in the USA, UK, Saudi Arabia and Kenya. Seroepidemiological studies have shown a worldwide distribution of this virus, including Japan, USA, UK, Southeast Asia, Canada, China and Kenya. This virus has been circulating in Sapporo for at least 19 years (1977-1995). HuCV/Sa/82/J strain is thought to be one of the common causes of viral gastroenteritis worldwide. The HuCV/Sa/82/J strain has been detected mainly in infants. Age-related prevalence of antibody to this strain also shows that infections commonly occur in children less than 5 years old, although viruses in the NV and SMA genogroups commonly infect adults. The pattern of acquisition of antibodies to strain HuCV/Sa/82/J is similar to that of other common viral infections. HuCV/Sa/82/J strain is unique virologically and clinically among caliciviruses.

Age Factors

Dot blot hybridization with a cDNA probe derived from the human calicivirus Sapporo 1982 strain.

A dot blot hybridization assay was developed for detection of human calicivirus/Sapporo/82/J (HuCV/Sa/82) or strains closely related to HuCV/Sa/82 in stool specimens. The cDNA derived from the RNA-dependent RNA polymerase (RDRP) region of HuCV/Sa/82 was used as a positive probe and the pBR322 DNA as a negative control probe. Both probes were labeled with digoxigenin and the products of hybridization reaction were detected with an anti-digoxigenin antibody-alkaline phosphatase conjugate. This assay was specific for HuCV/Sa/82 and for HuCV antigenically related to HuCV/Sa/82. The lower limit of sensitivity of this assay was estimated to be about 10(5) physical particles or 10 pg of cDNA, similar to that of the previously developed ELISA for HuCV. In 1273 stool specimens obtained from children with acute gastroenteritis in Sapporo, Japan, 110 (8.6%) contained small round structured viruses by EM and 23 (1.8%) were positive for HuCV antigenically related to HuCV/Sa/82 by either the hybridization assay or ELISA. A higher positive rate was obtained with the dot blot assay (21%) than by ELISA (10%), suggesting that the dot blot assay either detects HuCV more broadly than the ELISA or detects HuCV covered with fecal antibodies which interrupt antigen-antibody reactions in the ELISA. Negative results for detection of Norwalk virus (NV) cDNA and feline calicivirus (FCV) RNA by both this assay and the ELISA indicated that the HuCV/Sa/82 strain is distinct antigenically and genetically from NV and FCV.

Acute Disease

Partial characterization of the genome of nine animal caliciviruses.

Caliciviruses (CVs) include at least 42 distinct serotypes. Seventeen CV serotypes have been isolated from marine sources and are called San Miguel sea lion caliciviruses (SMSVs). CVs also have been isolated from reptiles, primates, and other terrestrial animals. Nucleotide sequences from portions of genome of prototype strains for six SMSV serotypes, the reptile CV, Cro-1, the cetacean CV, Tur-1, and the primate CV, Pan-1, are presented. cDNA products of the polymerase (all strains characterized) and capsid (SMSV-17) regions were produced by reverse transcription-polymerase chain reaction using Pan-1 primers. Comparisons of nucleotide and amino acid identity among these and published CV sequences indicated that the nine characterized CVs fall into a phylogenetic group that includes SMSV-1 and SMSV-4 and that is more closely related to other characterized animal CVs than to most human CVs. The phylogenetic analysis also indicated that distinct genera exist among the Caliciviridae. SMSV-17 and SMSV-4 are predicted to be closer to each other than other caliciviruses of known serotype; 574 (82%) of the 704 amino acids in the SMSV-17 and SMSV-4 capsid genes were identical.

Amino Acid Sequence