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B Grinde

Publications and source records attributed to B Grinde.

At least 19 recordsLinked to original sources
PubMed2002

Molecular epidemiology of TTV-like mini virus in Norway.

TT virus (TTV), the first human circovirus to be discovered, appears to be present in most people; less is known about the prevalence of the related TTV-like mini virus (TLMV). A sensitive nested PCR, specific for TLMV, detected the virus in 48% of 201 sera (Norwegian blood donors) previously found to have a 90% prevalence of TTV. More samples were either positive for both or negative for both viruses than what would have been expected from a random distribution (p = 0.08). Sequence analysis revealed considerable heterogeneity of Norwegian TLMV as compared to international sequences, suggesting that TLMV is efficiently dispersed in human populations.

Blood Donors↗
PubMed2001

High prevalence of TT virus-related DNA (90%) and diverse viral genotypes in Norwegian blood donors.

Early estimates of the prevalence of TTV viremia in healthy adults of developed countries were in the order of 1--10 %, while similar estimates in Third World countries were considerably higher. Using three different PCRs, TTV-related DNA was detected in serum from 180 out of the 201 Norwegian blood donors tested, indicating that these viruses are almost universally present in adults. Sequence analysis revealed heterogeneity similar to what is found world-wide. The data suggest that the previous discrepancy in prevalences might be related to a lower serum concentration of virus in developed countries. The high prevalence adds evidence to the benign nature of the virus.

Adolescent↗
PubMed2001

Molecular epidemiology of calicivirus infections in Norway.

The national reference laboratory for calicivirus diagnostics monitors the epidemiology of calicivirus infections in Norway. During winter 1998-1999, 406 fecal samples were received from patients with suspected calicivirus infection. Of these, 76 (19%) were calicivirus positive by a nested reverse transcription-polymerase chain reaction. A number of alternative PCR designs were employed to disclose false negatives, but none were found. One half of the PCR positive samples were sequenced in order to investigate whether various cases represented the same outbreak, and to what extent a single or multiple subtypes were responsible for the morbidity during this season. The sequence data revealed that the majority of cases represented a genotype related to the Lordsdale strain, whereas the remaining cases seemed more sporadic. Most often, samples from particular outbreaks were highly homogeneous. However, in a few cases, samples connected with the same outbreak proved to contain epidemiologically independent strains.

Caliciviridae↗
PubMed2000

Intersubtype recombinant HIV type 1 involving HIV-MAL-like and subtype H-like sequence in four Norwegian cases.

Suspected epidemiological links between three cases of human immunodeficiency virus type 1 (HIV-1) infection were verified by the finding of a shared unique virus genotype. A probable male index case was not available for testing. Case 1 was a female sexual partner of the index case. Case 2 was an adult son of case 1. Case 3 was a female sexual partner of case 2. The link to the index case was substantiated by the subsequent finding of another female sexual contact of the index case, harboring the same HIV-1 genotype as the three other cases. To characterize the genotype further, the complete provirus nucleotide sequence was obtained directly from blood cell DNA of case 3. HIV cultivated from case 3 demonstrated CCR5 dependence, an extreme slow-low phenotype, and some genotypic features not present in its directly sequenced counterpart. Most of the gag, pol, and vif genes of these viruses clustered with one of the earliest African HIV-1 strains, MAL, previously classified as a recombinant between the subtypes A, D, and I. Most of the rest of the genome was related to subtype H, albeit with less than 90% identity in most regions. These viruses are the only ones shown to display extensive similarity with MAL in the gag-pol region and among the first HIV-1 recombinants described involving subtype H. We postulate that the gag-pol genes of MAL and these viruses are derived from a common ancestor that is not necessarily intersubtype recombinant in the pol region.

Adult↗
PubMed2000

Molecular epidemiology of viral infections. How sequence information helps us understand the evolution and dissemination of viruses.

Viruses evolve much faster than cellular organisms. Together with recent advances in nucleic acid sequencing and biocomputing, this allows us to distinguish between related strains of viruses, and to deduce the relationships between viruses from different outbreaks or individual patients. Databases of nucleotide sequences contain a large number of viral sequences with which novel sequences from local outbreaks can be compared. In this way the dissemination of viruses can be followed both locally and globally. We here review the biological and technological background to the use of virus nucleic acid sequences in epidemiological studies, and provide examples of how this information can be used to monitor human viruses. Molecular studies are particularly valuable for understanding the dissemination and evolution of viruses. The knowledge obtained is useful in epidemiological reconstructions, in real-time surveillance, and may even enable us to make predictions about the future developments of viral diseases.

Animals↗
PubMed1999

Mutations designed to alter the stability of a putative RNA duplex in the HIV-1 pol gene.

In the HIV-1 integrase coding region there is a polypurine tract (PPT) involved in the initiation of provirus plus-strand synthesis. Upstream of this PPT there is a 15-nucleotide inverted repeat (IR) complementary to most of the PPT. We have constructed one mutant with five amino acid-neutral U to C and A to G changes in the IR and one mutant with corresponding amino acid-neutral changes in the PPT. Each set of changes abolished the complementarity and suppressed the replication of HIV-1 slightly. The combination of these ten changes restored the complementarity, and doubled the calculated free energy of the putative duplex between the IR and the PPT. This double mutant did not replicate under normal conditions, possibly because the reverse transcriptase was unable to penetrate the duplex. However, when high loads of the double mutant were added to permissive cells, replicative HIV did occasionally appear. The resurrected virus harvested from these cells replicated consistently, even though the ten nucleotide changes were left unchanged. There were no compensatory mutations in the vicinity of the IR/PPT or in the reverse transcriptase gene.

Animals↗
PubMed1999

CAG repeats in various organisms studied by Southern blot analysis.

A 90-nucleotide (CAG)30, single-stranded DNA was used to probe Southern blots in order to indicate the quantity and distribution of long CAG repeats in selected genomes. Bovine and rat genomes were found to contain a particularly high content of CAG repeats, while the repeats were comparatively rare in the human genome. A particularly strong signal in the bovine genome was due to a CAG repeat associated with the 1.709 satellite. A similar element was found in goat and musk, but not in the other artiodactyls tested, suggesting that this particular CAG repeat developed some 10-20 million years ago within a 3.8-kb unit presently belonging to the satellite element and that this unit has later multiplied in the genome. Single-copy repeats could be discerned in yeast, but not in mammals. Thus the probe did not detect specific repeats in patients with CAG repeat diseases.

Animals↗
PubMed1998

The estimated impact of the CCR-5 delta32 gene deletion on HIV disease progression varies with study design. Oslo HIV Cohort Study Group.

OBJECTIVES: To study the impact of the genotype CCR-5 wild-type +/A32 on the progression rate to AIDS and death, and to discuss sources of bias according to study design. METHODS: A prospective study of 310 HIV-positive subjects with follow-up time from study entry (prevalent cohort), and a prospective study of 105 HIV-positive subjects with well-defined time of HIV seroconversion, with follow-up time from the retrospectively assessed date of HIV seroconversion (retrospective incident cohort). RESULTS: Slower progression to AIDS among subjects with CCR-5 +/delta32 than those with CCR-5 +/+ genotype was estimated in the prevalent cohort (P=0.07, log-rank test). Slower progression to death from any cause was also estimated for subjects with CCR-5 +/delta32 (P < 0.05, log-rank test). No differences in survival after AIDS diagnosis were seen (P=0.89, log-rank test). No differences in the progression rate to AIDS (P=0.82, log-rank test) or death (P=0.78, log-rank test) were estimated in the retrospective incident cohort. CONCLUSIONS: The varying estimates of the impact of CCR-5 genotype on progression to AIDS in this and other studies, may be real and reflect differences in the dependence of HIV on the CCR-5 receptor, or may be due to systematic errors caused by study design. Several methodological difficulties occur when the factor studied, such as CCR-5 genotype, is associated both with the risk of being HIV-infected and the progression of disease.

Acquired Immunodeficiency Syndrome↗
PubMed1998

A unique hepatitis A virus strain caused an epidemic in Norway associated with intravenous drug abuse. The Hepatitis A Study Group.

A major epidemic of hepatitis A virus (HAV), associated with intravenous drug abuser (IVDA) communities, was studied by molecular epidemiology using a 348 bp region of the VP1/2PA junction of the HAV genome. A total of 621 cases were notified during the 2-year epidemic, 492 of whom were IVDA. Serum samples, taken from 79 patients during the acute phase of infection, were selected for analysis of HAV RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing. A unique epidemic strain was detected among 49 cases thought to be associated with the epidemic, and among 10/30 patients with no apparent association to the epidemic. The other 20 HAV variants differed from the epidemic strain, and in several cases could be connected to the patient's destination of travel. These strains were mostly associated with smaller outbreaks that were soon eradicated. Our data indicate different dissemination routes of HAV, suggesting that needle sharing practises contribute to a wide spread of the virus in the IVDA communities. By early detection of an outbreak, by epidemic survey and sequence analysis, preventive measures can be applied, and thereby limit the epidemic at an early stage.

Disease Outbreaks↗
PubMed1998

Prolonged nosocomial outbreak of hepatitis A arising from an alcoholic with pneumonia.

From April to June 1996, an outbreak of hepatitis A virus (HAV) infection affecting 15 nurses, patients and household contacts occurred in the Department of Internal Medicine at Aker University Hospital, Oslo. The index case was a homeless alcoholic who was hospitalized in March 1996 with pneumonia while simultaneously incubating HAV infection. Four secondary cases were infected by the index case, while another 10 cases were caused by a continuous spread of infection within the department during the following months. Sequence of the VP1/P2A junction of HAV was obtained from 9 patients, including the index case, and all sequences were identical to each other. Mass vaccination of hospital employees with a formalin-inactivated HAV-vaccine took place in late May, and following this the outbreak stopped. Several factors probably combined to account for this unusual outbreak, e.g. an index case unsuspected of incubating with HAV infection, and a low prevalence rate of protective antibodies to HAV among the hospital staff.

Adult↗
PubMed1998

The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe.

The chemokine receptor CCR5 is encoded by the CMKBR5 gene located on the p21.3 region of human chromosome 3, and constitutes the major co-receptor for the macrophage-tropic strains of HIV-1. A mutant allele of the CCR5 gene, Delta ccr5 , was shown to provide to homozygotes with a strong resistance against infection by HIV. The frequency of the Delta ccr5 allele was investigated in 18 European populations. A North to South gradient was found, with the highest allele frequencies in Finnish and Mordvinian populations (16%), and the lowest in Sardinia (4%). Highly polymorphic microsatellites (IRI3.1, D3S4579 and IRI3.2, D3S4580 ) located respectively 11 kb upstream and 68 kb downstream of the CCR5 gene deletion were used to determine the haplotype of the chromosomes carrying the Delta ccr5 variant. A strong linkage disequilibrium was found between Delta ccr5 and specific alleles of the IRI3.1 and IRI3.2 microsatellites: >95% of the Delta ccr5 chromosomes carried the IRI3.1-0 allele, while 88% carried the IRI3.2-0 allele. These alleles were found respectively in only 2 or 1.5% of the chromosomes carrying a wild-type CCR5 gene. From these data, it was inferred that most, if not all Delta ccr5 alleles originate from a single mutation event, and that this mutation event probably took place a few thousand years ago in Northeastern Europe. The high frequency of the Delta ccr5 allele in Caucasian populations cannot be explained easily by random genetic drift, suggesting that a selection advantage is or has been associated with homo- or heterozygous carriers of the Delta ccr5 allele.

Acquired Immunodeficiency Syndrome↗
PubMed1998

A common RNA motif in the 3' end of the genomes of astroviruses, avian infectious bronchitis virus and an equine rhinovirus.

In the 3' non-coding region of the genomes of infectious bronchitis virus, an avian coronavirus and the picornavirus equine rhinovirus serotype 2, there is a motif with remarkable similarity, both in sequence and folding, to the second RNA stem-loop from the 3' end of the genomes of human astroviruses. This motif was also found in astroviruses of sheep, pig and turkey, suggesting that it is a common feature of all astroviruses. The conserved nature of the motif indicates that there has been strong selection for its preservation. There is significant homology between the regions flanking this motif in infectious bronchitis virus and a continuous RNA sequence at the same distance from the 3' poly(A) tail in some related mammalian coronaviruses. These observations suggest that the presence of the motif in these three viral families is the result of at least two separate RNA recombination events.

Animals↗
PubMed1997

Sequence analysis of HIV-1 group O from Norwegian patients infected in the 1960s.

Three Norwegians, a couple and their daughter, died from AIDS in 1976 after up to 10 years of clinical manifestations of HIV infection (Lindboe et al., 1986, Acta Pathol. Microbiol, Immunol. Scand. 94, 117-123; Frøland et al., 1988, Lancet i, 1344-1345). We here demonstrate the presence of HIV DNA in autopsy materials from the father and the daughter. In phylogenetic analysis, the obtained sequences of the HIV pol and vif genes clustered with the HIV-1 group O clade. The genotyping was confirmed by detection of antibodies against HIV-1 group O in blood samples from the father and the mother. That these and other early isolates of HIV-1 are very similar to the presently circulating viruses and not intermediates between the present subtypes, verifies that the latest common ancestor of HIV-1 existed long before the emergence of the present epidemic. The presence of HIV-1 group O 30 years ago suggests that the limited spread of these viruses, compared to HIV-1 group M viruses, is not due to a later emergence of the group O viruses.

Base Sequence↗
PubMed1997

[An outbreak of hepatitis A among intravenous drug addicts in Oslo 1995-96].

Intravenous drug abuse is a well-known risk factor for acquiring hepatitis A infection. Among drug abusers most cases are sporadic, but epidemic outbreaks may occur occasionally. In this article we describe an epidemic outbreak including 144 serologically proved cases of hepatitis A among intravenous heroin and amphetamine abusers in Oslo. The outbreak lasted for 11 months. 59 (41%) of the patients were admitted to hospital. One of them died and seven developed severe but reversible acute hepatitis. We also registered 26 cases of hepatitis A among close contacts, 14 of whom were associated with a nosocomial outbreak that affected nurses, fellow patients and relatives. We do not know how the hepatitis A virus was introduced into the abuser population, but the further spread was probably dominated by a combination of faecal-oral transmission and parenteral transmission secondary to sharing needles. Although we were unable to detect hepatitis A virus in confiscated drug samples by means of polymerase chain reaction we cannot exclude that some abusers were infected by injection of contaminated amphetamine.

Adult↗
PubMed1997

Characterisation of an epidemic of hepatitis A virus involving intravenous drug abusers--infection by needle sharing?

An epidemic of hepatitis A virus (HAV) among intravenous drug abusers in Oslo involved 144 serologically confirmed cases. Another 26 patients (non-drug abusers), of whom 14 were derived from a single nosocomial outbreak, were associated with the epidemic. Sequencing of the VP1/P2A junction revealed that viruses associated with the epidemic were completely identical, whereas other HAV samples collected during the same period differed by up to 10%. HAV was detected in the serum of 48 of 100 patients by a nested PCR. Viremia was observed as early as 25 days before the onset of clinical hepatitis, and up to 30 days after. The large number of patients within the drug abuser group, and the few secondary cases, raised the question of whether the virus could be transmitted by the use of needles. To establish whether viral contamination of drugs did contribute appreciably to maintaining the epidemic, we examined heroin and amphetamine confiscated during the period, using immunomagnetic separation coupled to nested PCR, but failed to detect any virus. Antibodies against hepatitis B virus and hepatitis C virus were common among the HAV infected drug abusers (43% and 81%, respectively), suggesting widespread sharing of needles. This observation and the large number of patients with a demonstrable viremia suggest that needle sharing may contribute to the dissemination of HAV.

Amphetamine↗
PubMed1997

Molecular characterisation of the 3'-end of the astrovirus genome.

We have sequenced the 3'-end of the RNA genomes of 14 serotyped and 12 untyped isolates of human astrovirus. The sequences, which include all 8 serotypes, were used to predict secondary structures, postulate possible functional domains, reveal conserved regions suitable for nucleic acid amplification and perform phylogenetic analysis. The final nucleotides of the capsid protein precursor gene and the adjacent 3'-noncoding region were highly conserved and, except for 35 nucleotides with homology to a sequence in the 3'-end of a coronavirus RNA genome, unique to astrovirus family. This confirms that the 3'-end is a suitable target for universal and specific detection of astrovirus RNA. For the deduced 72 C-terminal amino acids of the capsid protein precursor, distances between the serotypes were found to vary from 0.1 substitution per site between serotypes 3 and 7 to more than one substitution per site between serotype 4 and the other serotypes. Different isolates of the same serotype were closely related, which indicates that the presently used type-specific antibodies differentiate between phylogenetically distinct groups. RNA secondary structures with minimal free energy were predicted using computer programs. Comparative sequence analysis verified the significance of certain of the predicted structural elements.

Base Sequence↗
PubMed1996

[The HIV proteinase--a target for antiviral agents].

The enormous resources spent on developing inhibitors of the HIV proteinase is finally proving worth while. The FDA in the USA approved saquinavir (Invirase, Roche) for treatment of AIDS in December 1995, and the presumably even more useful inhibitors, ritonavir (Norvir, Abbott) and indinavir (Crixivan, Merck) in March 1996. The clinical trials indicate that these substances are more efficient antiviral agents than the well known reverse transcriptase inhibitors (e.g., AZT or ddC). In the present article, the function of the HIV proteinase will be discussed, as well as the drug design strategies leading to the success. We believe that the combination of biotechnology and computer modelling is a potent tool for designing drugs, and that these proteinase inhibitors not only signal optimism in the treatment of AIDS, but also a new era in the development of therapeutics.

Antiviral Agents↗