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PubMed2004

Differences in hepatitis C virus core protein processing among genotypes 1 and 2.

Two forms of hepatitis C virus (HCV) core protein, p23 and p21, are produced from a precursor polyprotein. Production of p21 by cleavage at the c-terminus of p23 is considered essential for viral assembly and replication. In the present experiment, an in vitro translation and transcription assays were used to examine cleavage of p21 from p23 among 19 clones isolated from patients with chronic hepatitis, including 10 infected with genotype 1, and nine infected with genotype 2. Significantly greater p21 to p23 ratios were observed among genotype 1 clones, compared to genotype 2 clones. A comparison of the amino acid sequences of these clones revealed greater production of p21 core protein among clones which contained alanine, rather than valine, at amino acid residue 189. An exploration of Hepatitis Virus Database revealed that efficient p21 production related alanine at amino acid position 189 was observed in most clones of genotype 1 and in rare clones of genotype 2. These data suggest that the efficiency of core protein production differs among genotypes depending on differences in the c-terminus amino acid sequences of their core region. This may explain differences in some of the clinical characteristics of various genotypes or clones.

Journal Article↗
PubMed2004

Apolipoprotein E genotype and changes in serum lipids and maximal oxygen uptake with exercise training.

Physical activity improves lipid levels by altering triglyceride (TG) metabolism. Apolipoprotein E (Apo E) facilitates TG clearance by mediating lipoprotein binding to hepatic receptors, but Apo E also has less defined roles in skeletal muscle and nervous tissue. This study examined if variants in Apo E genotype affect the lipid and physiologic response to exercise training. Seven centers genetically screened 566 individuals to recruit 120 subjects into 6 gender-specific cohorts equal for the most common Apo E genotypes: E2/3, E3/3, and E3/4. Anthropometics, exercise capacity (Vo(2)max), serum lipids, and post heparin (PH) plasma lipase activities were measured before and after 6 months of supervised exercise training. Difference in the response (Delta) to training among the Apo E genotypes was the primary outcome variable. Differences in pretraining serum lipids among the Apo E genotypes mimicked those observed in population studies: TGs were slightly higher in E2/3 subjects, whereas low-density lipoprotein (LDL)-cholesterol (C) was lower (P = not significant [NS] ). TGs decreased 11% with training for the entire cohort (P <.0001) and 7%, 12%, and 14% for the Apo E 2/3, 3/3 and 3/4 groups, respectively (P = NS for Delta). LDL-C did not change in the entire cohort, but decreased slightly in the 2/3 and 3/3 subjects and increased 4% in the 3/4 group (P = NS for Delta). High-density lipoprotein (HDL)-C increased 2% for the entire cohort (P =.06) due to a 6% increase in the 3/3 group (P =.07 for Delta). Total cholesterol (TC)/HDL and LDL/HDL decreased with training in the 2/3 and 3/3 groups, but increased in the 3/4 subjects and these responses differed among the genotypes (P <.05 for Delta). Vo(2)max increased 9% to 10% for the entire cohort, but only 5% in the 3/3 subjects versus 13% in the 2/3 and 3/4 groups and these differences were significantly different among the genotypes (P <.01 for Delta). This is the first prospective study to demonstrate that the serum lipid response to exercise training differs by Apo E genotype in a pattern consistent with known metabolic differences among the variants. Surprisingly, Apo E genotype also affected the increase in aerobic capacity produced by exercise training possibly via undefined effects on nerve and skeletal muscle function.

Adult↗
PubMed2003

Association of the SNP-19 genotype 22 in the calpain-10 gene with elevated body mass index and hemoglobin A1c levels in Japanese.

BACKGROUND: An association of variations in the calpain-10 gene (CAPN10) with type 2 diabetes was originally reported in Mexican Americans. However, some studies in other racial groups were contradictory. METHODS: We studied the influence of genotypes and haplotype combinations (haplogenotypes) of CAPN10 on the metabolic traits in 286 Japanese subjects who visited a General Health Check-up Center. RESULTS: As for single nucleotide polymorphism (SNP)-19, subjects with genotype 22 had higher body mass index (BMI) and hemoglobin A(1c) (HbA(1c)) levels than those with genotypes 11 and 12 (p=0.003 and p=0.024, respectively). In SNP-63, subjects with genotype 11 had higher BMI and HbA(1c) levels than those with genotypes 12 and 22 (p=0.003 and p=0.045, respectively). Subjects who had genotype 22 at SNP-19 always had genotype 11 at SNP-63. Subjects with haplogenotype 121/121 had higher BMI levels (p=0.021) and tended to have higher HbA(1c) levels (p=0.08) than those with other haplogenotypes. All things considered, SNP-19 genotype 22, which was composed of haplogenotype 121/121 and 121/221, had highest significance level of association with elevated HbA(1c) levels. SNP-43 did not affect metabolic traits in our subjects. Subjects with haplogenotype 112/121 rather showed lower BMI and HbA(1c) levels (p=0.016 and p=0.008) than those with all other haplogenotypes. CONCLUSIONS: These results indicate the contribution of SNP-19 in CAPN10 to mild obesity and glucose intolerance in Japanese.

Blood Glucose↗
PubMed1998

HCV genotypes in Northern Italy: a survey of 1368 histologically proven chronic hepatitis C patients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) easily undergoes genomic changes, thus accounting for the presence of different genotypes, with different geographic distributions and different outcomes of chronic hepatitis. Type 1b is frequently found in advanced diseases; however, since this genotype is the most prevalent in older patients, the association with advanced age and severity of the disease is confounding. The aim of this study was to assess changes in the prevalence of HCV genotypes by surveying a large population of chronic hepatitis C patients in Northern Italy, and to assess if the high prevalence of genotype 1b in older patients with advanced diseases simply reflects the duration of HCV infection, rather than intrinsic biological properties of HCV. METHODS: We studied 1368 HCV-RNA positive patients, with histologically proven chronic hepatitis. Drug addiction, blood transfusions and sporadically acquired infections represented the risk factors. RESULTS: Genotype 1b, the most prevalent isolate, and genotype 2a were associated with older age, cirrhosis, sporadically-acquired infections and blood transfusion, while types 1a, 3a, and 4 were associated with younger age, chronic persistent hepatitis and drug addiction. Patients with a history of transfusions were divided into four groups depending on the period of transfusion. The prevalence of genotype 1b decreased with time. Type 3a appeared only after 1979. CONCLUSION: The severity of chronic hepatitis C could be related more to the duration of the infection rather than to the intrinsic pathogenicity of HCV genotypes.

Adolescent↗
PubMed2002

TT virus of certain genotypes may reduce the platelet count in patients who achieve a sustained virologic response to interferon treatment for chronic hepatitis C.

The platelet count increases after a sustained response to interferon (IFN) treatment for chronic hepatitis C (CH-C). However, the extent of the increase differs by patient. We investigated whether concurrent TT virus (TTV) infection interferes with the improvement of thrombocytopenia. Serial serum samples were obtained from 85 noncirrhotic CH-C patients who achieved a sustained virologic response for hepatitis C virus (HCV) upon IFN treatment, and tested for TTV DNA by three polymerase chain reaction (PCR) methods (UTR, N22 and TTV genotype-1). UTR PCR can detect essentially all TTV genotypes, whereas N22 PCR primarily detects four major TTV genotypes (1-4). Eighty-four patients (84/85, 99%) were positive for TTV DNA by UTR PCR, 27 (32%) by N22 PCR and 18 (21%) by TTV genotype-1 PCR just before IFN treatment was started (baseline). A sustained virologic response for TTV was observed in 6% (5/84) by UTR PCR, 52% (14/27) by N22 PCR and 56% (10/18) by TTV genotype-1 PCR. The platelet count was significantly lower in the N22 PCR-positive group than in the N22 PCR-negative group not only at baseline (14.9+/-3.8 vs. 18.1+/-6.4x10(4)/&mgr;l, P<0.05), but also at the non-HCV-viremic state one year after the completion of IFN treatment (15.5+/-2.8 vs. 18.6+/-5.5x10(4)/&mgr;l, P<0.05), the differences also being statistically significant by TTV genotype-1 PCR, but not by UTR PCR. These results suggest that certain TTV genotypes including genotype 1 may play a role in aggravating the thrombocytopenia of CH-C patients, either alone or in concert with HCV.

Journal Article↗
PubMed2003

Prevalence and characterization of hepatitis C virus genotype 4 in Japanese hepatitis C carriers.

Hepatitis C virus (HCV) can be classified into six major genotypes, the prevalences of which differ around the world. In Japan, the main genotypes are HCV 1 and HCV 2; others are found only rarely. Little is known about the prevalence in Japan of HCV genotype 4 which, is found frequently in North and Central Africa and the Middle East. Thus, we conducted a study to clarify distribution of HCV genotype 4 and the clinical demographics of patients with HCV genotype 4 in Japan. We examined HCV genotypes in 899 Japanese individuals with HCV viremia living in Aichi Prefecture, including 63 hemophiliacs. Four patients (0.4%) were infected with HCV genotype 4. All four of these patients were male hemophiliacs who had received clotting factors from foreign countries. Three patients were co-infected with human immunodeficiency virus (HIV); none were co-infected with GB virus-C/hepatitis G virus. Phylogenetic analysis of the El region indicated that all four patients were infected with subtype 4a. This subtype is related genetically to a subtype previously reported in Japanese and Italian hemophiliacs. HCV genotype 4 is indeed rare in Japan and may be detected only among hemophiliacs who have received inactivated clotting factor concentrates from foreign countries.

Journal Article↗
PubMed2000

Dopaminergic drug response and the genotype (Taq IA polymorphism) of the dopamine D2 receptor.

The genotype of the receptor with which a particular drug interacts may be a between- subject factor that modifies the pharmacodynamic and consequently the therapeutic response to drugs. Subjects with A1 allele (Taq IA restriction fragment length polymorphism) of the gene encoding for the dopamine D2 receptor (DRD2) seem to express lower number of DRD2 compared to subjects who do not have this allele. We investigated whether subjects homozygous for the A1 allele of the DRD2 gene have decreased response to DRD2 stimulation by apomorphine when compared with those homozygous for the A2 allele. Two hundred and two Caucasian subjects were genotyped for DRD2 Taq IA polymorphism, 6.9 % had the genotype A1A1 and 65% A2A2. Nine homozygous subjects/group were selected for the apomorphine study. Five, 10 and 20 &mgr;g/kg of apomorphine were administered subcutaneously according to a randomized crossover design. The main pharmacodynamic criterion was the plasma growth hormone increase induced by apomorphine. Secondarily, we measured oral temperature responses and yawns in response to apomorphine. Plasma apomorphine concentrations were similar for the two matched and only genotypically different groups. Apomorphine dose-dependently increased serum growth hormone concentration, and significant effect of time, dose by time interaction but no effect of genotype or genotype by dose interaction was shown. Apomorphine decreased body temperature, significant effect of dose, time, dose by time interaction but no effect of genotype or genotype by dose interaction were observed. The number of apomorphine-induced yawns increased dose-dependently but no significant difference between groups occurred. Thus, in this study apomorphine-induced responses were not modified by DRD2 Taq IA polymorphism although the power of the study could be insufficient to detect subtle differences.

Journal Article↗
PubMed1997

Hepatitis C virus genotypes and liver disease in patients undergoing allogeneic bone marrow transplantation.

Hepatitis C virus (HCV) genotypes were investigated in 57 HCV-infected patients undergoing allogeneic BMT at four European BMT units where death resulting from liver failure (LF) in HCV-infected patients varied from < 1% to > 80%. The aim of the study was to determine whether differing HCV genotypes could account for the different severity of post-transplant liver disease (LD). Sera from patients with pre (n = 22) or post-BMT (n = 35) HCV infection were collected from Italy (Genova, Monza), Sweden (Huddinge) and Germany (Ulm). Patients were grouped as follows: LF: 19/57; acute hepatitis (AH): 10/57 or chronic hepatitis (CH): 22/57; no liver disease (LD): 6/57. HCV genotypes were identified by hybridisation of the 5'UTR amplified products with type-specific oligonucleotides probes according to Simmonds (Hepatology 1994; 19: 1321-1324). Genotype HCV 1 was identified in 34 patients (60%), HCV 2 in 15 (26%), HCV 3 in three (5%), mixed infection in three (5%) and undefined in two (3.5%). In the LF group HCV 1 was identified in 10/19 and other genotypes in 9/19. Median timing of LF was earlier in patients infected with HCV 1 compared to other genotypes (45 and 68 days, respectively), largely due to the cause of LF; death from veno-occlusive disease (VOD) and hepatitis occurred at 30 and 68 days post-BMT, respectively. Genotype 1 was also identified in cases with no LD. These data indicate that there was no evident correlation between HCV genotype and type or severity of post-transplant liver disease.

Adolescent↗
PubMed2002

Molecular characterisation of sweet cherry (Prunus avium L.) genotypes using peach [Prunus persica (L.) Batsch] SSR sequences.

A total of 76 sweet cherry genotypes were screened with 34 microsatellite primer pairs previously developed in peach. Amplification of SSR loci was obtained for 24 of the microsatellite primer pairs, and 14 of them produced polymorphic amplification patterns. On the basis of polymorphism and quality of amplification, a set of nine primer pairs and the resulting 27 informative alleles were used to identify 72 genotype profiles. Of these, 68 correspond to unique cultivar genotypes, and the remaining four correspond to three cultivars that could not be differentiated from the two original genotypes of which they are mutants, and two very closely related cultivars. The mean number of alleles per locus was 3.7 while the mean heterozygosity over the nine polymorphic loci averaged 0.49. The results demonstrate the usefulness of cross-species transferability of microsatellite sequences allowing the discrimination of different genotypes of a fruit tree species with sequences developed in other species of the same genus. UPGMA cluster analysis of the similarity data divided the ancient genotypes studied into two fairly well-defined groups that reflect their geographic origin, one with genotypes originating in southern Europe and the other with the genotypes from northern Europe and North America.

Microsatellite Repeats↗
PubMed2003

Influence of oxygen administration on pulmonary haemodynamics and tissue oxygenation during exercise in COPD patients with different ACE genotypes.

We previously found that the angiotensin-converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance of tissue oxygenation during exercise in chronic obstructive pulmonary disease (COPD) patients. This study was designed to compare the effect of oxygen administration on pulmonary haemodynamics and tissue oxygenation during exercise in COPD patients with different ACE genotypes. Forty-three COPD patients (II=16, ID=12, DD=15) underwent right heart catheterization, and then performed an exercise test with room air or oxygen. We measured pulmonary haemodynamic variables and indices of tissue oxygenation such as mixed venous oxygen tension (PVO2) and arterial lactate concentration, both at rest and after exercise. The magnitude of difference in mean pulmonary arterial pressure and pulmonary vascular resistance after exercise between breathing of room air and breathing of oxygen did not significantly differ among the three groups. PVO2 after exercise with room air or oxygen was significantly higher in patients with the II genotype than in those with the ID or DD genotype. In contrast, lactate concentration after exercise with room air or oxygen was significantly lower in patients with the II genotype than in those with the ID or DD genotype. Moreover, the magnitude of difference in PVO2 and lactate concentration after exercise between breathing of room air and breathing of oxygen was the II>ID>DD genotype. These findings suggest that the ability of oxygen administration to improve tissue oxygenation during exercise is associated with the ACE genotypes in COPD patients.

Administration, Inhalation↗
PubMed2004

GERBIL: Genotype resolution and block identification using likelihood.

The abundance of genotype data generated by individual and international efforts carries the promise of revolutionizing disease studies and the association of phenotypes with individual polymorphisms. A key challenge is providing an accurate resolution (phasing) of the genotypes into haplotypes. We present here results on a method for genotype phasing in the presence of recombination. Our analysis is based on a stochastic model for recombination-poor regions ("blocks"), in which haplotypes are generated from a small number of core haplotypes, allowing for mutations, rare recombinations, and errors. We formulate genotype resolution and block partitioning as a maximum-likelihood problem and solve it by an expectation-maximization algorithm. The algorithm was implemented in a software package called GERBIL (genotype resolution and block identification using likelihood), which is efficient and simple to use. We tested GERBIL on four large-scale sets of genotypes. It outperformed two state-of-the-art phasing algorithms. The phase algorithm was slightly more accurate than GERBIL when allowed to run with default parameters, but required two orders of magnitude more time. When using comparable running times, GERBIL was consistently more accurate. For data sets with hundreds of genotypes, the time required by phase becomes prohibitive. We conclude that GERBIL has a clear advantage for studies that include many hundreds of genotypes and, in particular, for large-scale disease studies.

Chromosome Mapping↗
PubMed2003

Cytomegalovirus (CMV) glycoprotein B genotypes and response to antiviral therapy, in solid-organ-transplant recipients with CMV disease.

Cytomegalovirus (CMV) can be classified into 4 glycoprotein B (gB) genotypes, on the basis of sequence variation in the UL55 gene. We assessed the effect that CMV gB genotype has on virologic and clinical response to therapy, in 50 solid-organ-transplant recipients with CMV disease. CMV loads were determined at regular intervals after the start of therapy. Genotype results were correlated with CMV-load kinetics in response to therapy with ganciclovir. At the onset of treatment, the distribution of CMV gB genotypes was as follows: gB1, 19/50 (38%); gB2, 9/50 (18%); gB3, 12/50 (24%); gB4, 2/50 (4%); and mixed-genotype infection, 8/50 (16%). Between viral genotype groups, time to clearance of CMV, failure to clear CMV, and calculated CMV-load half-life after the start of therapy were not significantly different. The CMV gB genotype did not affect the rate of disease recurrence or occurrence of tissue-invasive disease. It appears that the gB genotype, which causes CMV disease, does not significantly influence CMV-load kinetics or clinical response to therapy.

Animals↗
PubMed1999

Effects of serotonin transporter promoter genotype on platelet serotonin transporter functionality in depressed children and adolescents.

OBJECTIVE: To investigate possible associations between serotonin transporter (5-HTT) promoter genotypic variants (l/l, l/s, and s/s) and differential regulation of platelet 5-HTT functionality parameters in a group of drug-naive depressed children and adolescents and healthy controls. METHOD: Children and adolescents with major depression (n = 18) defined by DSM-III-R criteria and normal controls (n = 21) were assessed both for platelet serotonin functionality and for genotypic variants on 5-HTT promoter region. Four parameters were considered: (1) serotonin uptake rate (Vmax); (2) serotonin dissociation constant (K(m)); (3) paroxetine binding and density of site (Bmax); and (4) paroxetine dissociation constant (Kd). RESULTS: Depressed children had lower Vmax and K(m). Control subjects with l/l genotype had significantly higher Vmax than control subjects with l/s and s/s genotype. Control subjects with l/l genotype also had significantly higher Vmax than their depressed homologs. In contrast, Vmax was not significantly different between depressed and nondepressed subjects who carried the other 2 genotypes. The 5-HTT promoter genotype, diagnoses, or their interaction had no effect on the other serotonin parameters. CONCLUSIONS: While showing a significant decrease of Vmax and K(m) in a group of drug-naive depressed children and adolescents, these data suggest that l/l genotype has a substantial effect on the decrease of Vmax during a depressive episode.

Adolescent↗
PubMed1997

Relation of hepatitis C virus genotypes to risk factors and hepatic disease in Spanish patients.

OBJECTIVE: To ascertain the prevalence of hepatitis C virus (HCV) genotypes in Spain and their distribution by risk factors. METHODS: The study covered 216 patients with hepatitis C. Of these, 63 were intravenous drug users (IVDU), 44 had received transfusions, and 30 were hemodialyzed, and in 79 the risk factors were unknown. Antibodies against HCV were detected by second-generation enzyme immunoassay (EIA) and confirmed by immunoblot. HCV RNA presence was investigated by reverse transcription---polymerase chain reaction (RT-PCR), and a reverse hybridization test of the amplifications was used for the genotyping. RESULTS: The most frequently encountered genotypes were 1b (48.1%), 1a (21.3%) and 3a (11.1%). HCV genotypes 1a (42.8%) and 3a (20.6%) were the most prevalent genotypes in IVDU patients, while 1b was the most frequent in patients with unknown risk factors (62.0%), transfused patients (68.1%) and hemodialyzed patients (50.0%). Mixed infections were detected in nine cases (4.1%); three appeared in IVDU patients (4.7% of the total IVDUs), two in transfused patients (4.5%) and four (50%) in patients with unknown risk factors. No statistically significant differences were found in average ages of the IVDU patients with different genotypes. Non-IVDU patients having genotype 3a presented the lowest average age of all. No significant statistical differences were observed in alanine aminotransferase levels among patient groups with different genotypes (p>0.05 in all cases). Subtype 1b was present in six of the seven cases of cirrhosis (85.7%) and in nine of the 18 cases of active chronic hepatitis (50.0%).

Journal Article↗
PubMed1996

Discordant results from hepatitis C virus genotyping by procedures based on amplification of different genomic regions.

We compared the results of genotyping hepatitis C virus (HCV) either by PCR amplification of the core region or by hybridization of PCR-amplified products of the 5' untranslated region (5'UTR assay). Serum samples from 144 Italian anti-HCV-positive patients (106 drug abusers and 38 patients with chronic viral liver disease but no history of drug abuse) were studied. The original core region assay described by Okamoto et al. (H. Y. Okamoto, Y. Sugiyama, S. Okada, K. Kurai, Y. Akahane, Y. Sugai, T. Tanaka, K. Sato, F. Tsuda, Y. Miyakawa, and M. Mayumi, J. Gen. Virol. 73:673-679, 1992) allowed genotyping of 75 of 144 samples. A modified version of Widell et al. (A. Widell, S. Shev, S. Månsson, Y.-Y. Zhang, U. Foberg, G. Norkrans, A. Frydén, O. Weiland, J. Kurkus, and E. Nordenfelt, J. Med. Virol. 44:272-279, 1994) allowed genotyping of 11 of 79 samples (50 of 79 samples remained unclassified by the method of Okamoto et al. In contrast, all 144 samples were genotyped by the 5'UTR assay. Forty-six of 75 (61 percent) of the samples genotyped by the method of Okamoto et al. and 10 of 11 (91 percent) of the samples genotyped by the method of Widell et al. had results consistent with those obtained by the 5'UTR assay. According to the results of direct sequencing, the method of Okamoto et al. erroneously classified seven samples as having mixed infections. In conclusion, HCV genotyping seems more reliable when it is performed by the 5'UTR assay than by either of two core region assays. The major advantage provided by the 5'UTR assay is a much lower proportion of negative or indeterminate results in younger patients with histories of drug abuse or infection by genotypes other than HCV type 1.

Adolescent↗
PubMed1997

Comparison of plasma virus loads among individuals infected with hepatitis C virus (HCV) genotypes 1, 2, and 3 by quantiplex HCV RNA assay versions 1 and 2, Roche Monitor assay, and an in-house limiting dilution method.

The accuracy of different methods for the quantitation of hepatitis C virus in plasma was measured with samples from individuals infected with different genotypes and by using RNA transcripts of predetermined concentrations. Highly reproducible results were observed upon repeat testing of samples by both the original version of the Chiron branched-DNA (bDNA) assay (Quantiplex RNA assay; bDNA-1) and the currently available version (Quantiplex HCV RNA 2.0 assay; bDNA-2). A greater variability was observed in the Roche Monitor assay (correlation coefficient of 0.537, compared with 0.942 and 0.964 for the bDNA-1 and bDNA-2 assays, respectively). Significant differences in the efficiency of detection of genotypes 1, 2, and 3 were observed for the bDNA-1 and Roche Monitor assays, whereas the bDNA-2 assay and nested PCR at limiting dilution were able to quantify genotypes with equal sensitivity. By quantifying RNA transcripts of different genotypes, the sensitivities of the Roche Monitor assay for sequences of the type 2 and type 3 transcripts were estimated to be 11 and 8% of those achieved for genotype 1. When correction factors based upon these results and those from quantitation of circulating viral RNA sequences in samples from blood donors were used, the genotype-specific differences in virus load in samples from blood donors were no longer observed, consistent with previous studies with corrected values from the bDNA-1 assay. These results suggest that many of the previous studies evaluating the effect of genotype and virus load on the response to interferon using methods such as the Roche Monitor assay and other competitive PCR methods require reinterpretation. Differences in efficiency of quantitation should be taken into account in future investigations of the relationship between genotype and virus load.

Genes, Viral↗
PubMed1999

Species and genotypic diversities and similarities of pathogenic yeasts colonizing women.

We examined the patterns of strain relatedness among pathogenic yeasts from within and among groups of women to determine whether there were significant associations between genotype and host condition or body site. A total of 80 yeast strains were isolated, identified, and genotyped from 49 female volunteers, who were placed in three groups: (i) 19 women with AIDS, (ii) 11 pregnant women without human immunodeficiency virus (HIV) infection, and (iii) 19 women who were neither pregnant nor infected with HIV. Seven yeast species were recovered, including 59 isolates of Candida albicans, 9 isolates of Candida parapsilosis, 5 isolates of Candida krusei, 3 isolates of Candida glabrata, 2 isolates of Saccharomyces cerevisiae, and 1 isolate each of Candida tropicalis and Candida lusitaniae. Seventy unique genotypes were identified by PCR fingerprinting with the M13 core sequence and by random amplified polymorphic DNA analysis. Of the nine shared genotypes, isolates from three different hosts were of one genotype and pairs of strains from different body sites of the same host shared each of the other eight genotypes. Genetic similarities among groups of strains were calculated and compared. We found no significant difference in the patterns of relatedness of strains from the three body sites (oral cavity, vagina, and rectum), regardless of host conditions. The yeast microflora of all three host groups had similar species and genotypic diversities. Furthermore, a single host can be colonized with multiple species or multiple genotypes of the same species at the same or different body sites, indicating dynamic processes of yeast colonization on women.

AIDS-Related Opportunistic Infections↗
PubMed1993

Hepatitis B virus genotype A rarely circulates as an HBe-minus mutant: possible contribution of a single nucleotide in the precore region.

The emergence of HBe-minus hepatitis B virus (HBV) mutants, usually through a UAG nonsense mutation at codon 28 of the precore region, helps the virus to survive the anti-HBe immune response of the host. Host and viral factors that predispose to the emergence of such mutants are not well characterized. The fact that the precore region forms a hairpin structure essential for the packaging of viral pregenomic RNA may explain the extremely high prevalence of the UAG mutation at codon 28. It converts a wobble U-G pair in the packaging signal between nucleotide 3 of codon 15 (CCU) and nucleotide 2 of codon 28 (UGG) into a U-A pair. Since genotype A of HBV has a CCC sequence at codon 15, the UAG mutation would, instead, disrupt a C-G pair present in the wild-type virus. This alteration was shown by transfection experiments to greatly compromise the packaging of pregenomic RNA. The implication of this finding was elucidated by molecular epidemiological studies. Genotype A was found to be the most prevalent genotype in the wild-type virus populations in France but was found in only 1 of the 46 isolates of HBe-minus mutants found there. These mutants were contributed chiefly by genotype D, the second most prevalent genotype in France, which is characterized by a CCU sequence at codon 15. The role of the single nucleotide at codon 15 was confirmed by the finding of the single genotype A isolate in which both wild-type and mutant viruses were present. Interestingly, nearly all of the mutants had a codon 15 sequence of CCU instead of the CCC present in the wild-type viruses. Our results suggest that genotype A of HBV rarely circulates as HBe-minus mutants, probably because of a requirement for a simultaneous sequence change at codon 15. These data, together with the virtual absence of genotype A in the Chinese samples examined, may provide some insights into the uneven prevalence of HBe-minus mutants in the world.

Base Composition↗