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PubMed2001

Genotypic and phenotypic evidence of different drug-resistance mutation patterns between B and non-B subtype isolates of human immunodeficiency virus type 1 found in Brazilian patients failing HAART.

We have investigated the phenotypic and genotypic susceptibility of 14 HIV-1 strains isolated from individuals failing HAART therapy to protease inhibitors (PI). Proviral and plasma viral pol gene fragment were amplified, sequenced and subtyped. Nine samples clustered with protease subtype B reference strains and the remaining samples were classified as non-B subtype corresponding to subtype F (n = 4) and subtype A (n = 1). Although all patients were treated with similar P1 drug regimen, the non-B subtype isolates did not present the L90M and 184V mutations and used mainly G48V and V82A/F to achieve drug resistance. A strong cross-resistance phenotype among all four PI was associated with the mutation L90M in the subtype-B isolates, and with G48V and V82A/F in the non-B counterparts. This observation revealed that the non-B viruses tested had specific genotypic characteristics contrasting with the subtype-B isolates.

Amino Acid Sequence↗
PubMed1997

Changes in the mRNAs encoding subtypes I, II and III sodium channel alpha subunits following kainate-induced seizures in rat brain.

Several lines of evidence underscore a possible role of voltage-gated Na+ channels (NaCH) in epilepsy. We compared the regional distribution of mRNAs coding for Na+ channel alpha subunit I, II and III in brains from control and kainate-treated rats using non-radioactive in situ hybridization with subtype-specific digoxigenin-labelled cRNA probes. Labelling intensity was evaluated by a densitometric analysis of digitized images. Heterogeneous distribution of the three Na+ channel mRNAs was demonstrated in brain from adult control rats, which confirmed previous studies. Subtype II mRNAs were shown to be abundant in cerebellum and hippocampus. Subtype I mRNAs were also detected in these areas. Subtype III mRNAs were absent in cerebellar cortex, but significantly expressed in neurons of the medulla oblongata and hippocampus. The three subtypes were differentially distributed in neocortical layers. Subtype II mRNAs were present in all of the layers, but mRNAs for subtypes I and III were concentrated in pyramidal cells of neocortex layers IV-V. During kainate-induced seizures, we observed an increase in Na+ channel II and III mRNA levels in hippocampus. In dentate gyrus, subtype III mRNAs increased 3 h after KA administration to a maximum at 6 h. At this latter time, a lower increase in NaCh III mRNAs was also recorded in areas CA1 and CA3. NaCh III overexpression in dentate gyrus persisted for at least 24 h. In the same area, NaCh II mRNAs were also increased with a peak 3 h after KA injection and a return to control levels by 24 h. No changes in NaCh I mRNAs were seen. The KA-induced up-regulation in NaCh mRNAs probably resulted in an increase in hippocampal neuronal excitability.

Animals↗
PubMed1989

Psychosocial functioning of learning-disabled children: replicability of statistically derived subtypes.

The PIC scores of 132 learning-disabled children between the ages of 6 and 12 years were investigated using Q-factor analysis, four hierarchical-agglomerative clustering techniques, and one iterative partitioning clustering technique. Results revealed excellent correspondence between the subtypes derived by all grouping methods in terms of both misclassifications and mean PIC profile similarity of the subtypes across techniques. The mean PIC profile of one subtype indicated normal psychosocial adjustment; a second subtype exhibited evidence of significant internalized psychopathology; a third subtype had a mean PIC profile suggestive of externalized psychosocial maladjustment. These subtypes were virtually identical to three subtypes reported by Porter and Rourke (1985) in another study of learning-disabled children. The results indicate that learning-disabled children comprise a heterogeneous population in terms of psychosocial functioning and that subtypes of learning-disabled children with similar patterns of socioemotional adjustment can be recovered reliably from this population across samples and statistical grouping techniques.

Child↗
PubMed1997

PNU-107484A with alpha isoform-dependent functional changes in alpha(x)beta2gamma2 subtypes of rat recombinant GABA(A) receptors.

1. We discovered a novel gamma-aminobutyric acidA (GABA(A)) receptor ligand displaying seemingly opposite functionalities, depending on the alpha isoform of the alpha(x)beta2gamma2 subtypes. PNU-107484A enhanced GABA-induced Cl- currents in the alpha1beta2gamma2 subtype, but inhibited the currents in the alpha3beta2gamma2 and alpha6beta2gamma2 subtypes, and its half-maximal concentrations in the subtypes were 3.1 +/- 0.5, 4.2 +/- 1, and 3.5 +/- 0.2 microM, respectively, without showing much dependency on alpha isoforms. 2. In the alpha1beta2 subtype, the drug at concentrations up to 40 microM showed no effect on GABA-induced Cl- currents, suggesting the requirement of the gamma subunit for its action. 3. PNU-107484A behaved like a positive allosteric modulator of the alpha1beta2gamma2 subtype with its binding site distinct from those for benzodiazepines, barbiturates and neurosteroids. With the alpha3beta2gamma2 subtype, the drug behaved like a non-competitive inhibitor of GABA, thus blocking Cl- currents by GABA alone or in the presence of pentobarbitone and neurosteroids. 4. It appears that PNU-107484A is a unique GABA(A) receptor ligand with alpha isoform-dependent functionalities, which may provide a basis for development of alpha isoform-selective ligands, and it could be useful as a probe to investigate the physiological roles of the various alpha isoform subtypes.

Allosteric Regulation↗
PubMed1994

Purification of a novel G-protein alpha 0-subtype from mammalian brain.

Three distinct G-protein alpha o-subtypes, i.e. alpha o1, alpha o2 and a newly observed 'alpha o3', are present in membranes of mammalian brain, each appearing as two isoforms on SDS/PAGE. Only alpha o1 and alpha o2 appear to be substrates for pertussis toxin (PTX) when membranes or partially purified proteins are examined. In order to elucidate the apparent PTX-resistance of the third alpha o-subtype, we purified alpha o3 from porcine and bovine brain membranes. During the purification procedures, alpha o3 occurred in its dissociated monomeric form and, together with beta gamma-complexes, as a heterotrimer. In a first attempt, we used purified G-protein alpha i/alpha o-mixtures to obtain a final separation of alpha o3. By using f.p.l.c. anion-exchange chromatography on a Mono Q column, complete separation of alpha i1 and alpha o2 was achieved. Partial resolution of alpha o1, alpha i2 and alpha o3 was observed; alpha o3 was eluted between alpha o1 and alpha i2. If alpha o-subunits free from alpha i contaminants were loaded on to the Mono Q column, all three alpha o-subtypes were resolved. The identity of the third subtype as an alpha o-subtype was confirmed by sequence analysis of tryptic fragments. All three alpha o-subtypes bound GTP[S]. Purified alpha o3 was ADP-ribosylated when subjected to PTX treatment in the presence of beta gamma-subunits, and on SDS/PAGE the mobility of alpha o3 was similar to that of ADP-ribosylated alpha o1. On the basis of results obtained with subtype-specific antibodies, the third alpha o-subtype is immunologically more related to alpha o1 than to alpha o2. Purified alpha o3 failed to reconstitute carbachol-mediated inhibition of Ca2+ current in PTX-pretreated SH-SY5Y-cells, whereas alpha o1 and alpha o2 did successfully restore this effect. We conclude that the novel alpha o3 forms differs from alpha o1 and alpha o2 in its primary structure and may be involved in signal-transduction pathways other than those described for alpha o1 and alpha o2.

Adenosine Diphosphate Ribose↗
PubMed1997

Inositol 1,4,5-trisphosphate receptor subtypes differentially recognize regioisomers of D-myo-inositol 1,4,5-trisphosphate.

The Ins(1,4,5)P3 regioisomers, Ins(1,4,6)P3 and Ins(1,3,6)P3, which can mimic the 1,4,5-arrangement on the inositol ring of Ins(1,4,5)P3, were examined for Ca2+ release by using four types of saponin-permeabilized cell possessing various abundances of receptor subtypes, with special reference to the relation of potency to receptor subtype. Ins(1,4,6)P3 and Ins(1,3,6)P3 were weak agonists in rat basophilic leukaemic cells (RBL cells), which possess predominantly subtype II receptors, with respective potencies of 1/200 and less than 1/500 that of Ins(1,4,5)P3 [the EC50 values were 0.2, 45 and more than 100 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively]. Similar rank order potencies were also evaluated for the displacement of [3H]Ins(1,4,5)P3 bound to RBL cell membranes by these regioisomers. However, they caused Ca2+ release from GH3 rat pituitary cells possessing predominantly subtype I receptors more potently; Ins(1,4,6)P3 and Ins(1,3,6)P3 evoked release at respective concentrations of only one-third and one-twentieth that of Ins(1,4,5)P3 (the EC50 values were 0.4, 1.2 and 8 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). In COS-1 African green-monkey kidney cells, with the relative abundances of 37% of the subtype II and of 62% of the subtype III receptor, potencies of 1/40 and approx. 1/200 for Ins(1, 4,6)P3 and Ins(1,3,6)P3 respectively were exhibited relative to Ins(1,4,5)P3 (the EC50 values were 0.4, 15 and approx. 80 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). In HL-60 human leukaemic cells, in spite of the dominant presence of subtype I receptors (71%), similar respective potencies to those seen with COS-1 cells were exhibited (the EC50 values were 0.3, 15 and approx. 100 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). These results indicate that these regioisomers are the first ligands that distinguish between receptor subtypes; the present observations are of significance for the future design of molecules with enhanced selectivity.

Animals↗
PubMed1999

Regional distribution of Y-receptor subtype mRNAs in rat brain.

Molecular cloning techniques have recently led to the identification of a growing number of neuropeptide Y-receptor subtypes, suggesting possible subtype-specific involvement in different physiological processes. Here we report the first study which determines and compares the mRNA expression of all four cloned functional Y-receptor subtypes (Y1, Y2, Y4 and Y5) in consecutive sections of the rat brain on a cellular level, using a uniform in situ hybridization technique. Our results demonstrate that Y-receptor subtype mRNA expression is widely distributed throughout the rat brain. Interestingly, coexpression of all four Y-receptors, at different levels, is particularly evident within the limbic system, including the hypothalamus, hippocampus, amygdala, piriform and cingulate cortices and tegmental areas, all of which are heavily involved in behaviour, emotion and homeostatic regulation. Particularly interesting is the demonstration that Y5-receptor mRNA expression always coincides with the presence of Y1-receptor mRNA (although not vice versa), possibly due to the overlapping organization and transcriptional control of their genes. However, it is also clear that several brain nuclei display preferential expression of one or a selective combination of Y-receptor subtype mRNAs. Furthermore, it is evident that there is regionalization of expression within certain loci which express all four receptor subtype mRNAs, particularly within the paraventricular and arcuate hypothalamic nuclei. Our results suggest that some of neuropeptide Y's (NPY) effects may be mediated through one particular subtype, whereas other physiological processes might require the coordinated action of different subtypes within the same or discrete areas.

Animals↗
PubMed2006

Neutralization epitope responsible for the hepatitis B virus subtype-specific protection in chimpanzees.

Neutralizing monoclonal antibody (BX-182) directed against the d determinant of hepatitis B virus (HBV) surface antigen protected chimpanzees from infection by HBV subtype adw but not by subtype ayw, as demonstrated by intravenously inoculating a mixture of the antibody with the respective subtype of the virus. To elucidate the mechanism underlying the subtype-specific protection, a combinatorial approach of screening random peptide phage libraries, bioinformatics, and structure analysis was used in this study to identify the neutralization epitope responsible for the observed protection. The epitope was mapped at the N terminus of the pre-S1 region of the hepatitis B surface antigen between residues 17 and 21, of which the residues Val-18/Pro-19 were critical for antibody binding. Alignment of amino acid sequences derived from diverse genetic variants of HBV revealed that the epitope was present in ad subtypes and in their corresponding genotypes A, B, C, F, and H. By contrast, this epitope was not found in a majority of ay subtypes or in genotypes D, E, and G, where the antigenic residues Val-18/Pro-19 within the epitope were replaced by Thr/Ser, Thr/Thr, or Ala/Ser, respectively, resulting in a drastic conformational change of the epitope. These data indicate that, by binding discriminately to the subtype "d" epitope in the pre-S1 region, neutralizing antibody BX-182 protects chimpanzees from HBV infection in a subtype-specific manner, suggesting a potential escape mechanism for HBV genetic variants.

Amino Acid Sequence↗
PubMed2005

The validity of the DSM-IV subtypes of attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine the validity of the three subtypes of ADHD defined by DSM-IV. METHOD: Studies published in English were identified through searches of literature databases. RESULTS: Estimates of the prevalence of ADHD have increased as a result of the introduction of DSM-IV criteria. Factor analytical and genetic studies provide some support for the validity of the distinction between the three subtypes. However, diagnosis of the combined subtype seems more reliable than the other two subtypes, although reliability is largely unknown for the latter. The hyperactive-impulsive subtype, the least common, differs from the other two subtypes in age distribution, association with other factors and neuropsychological parameters. Almost all treatment trials are based on participants with the combined type. CONCLUSION: Data supporting the validity of the inattentive and hyperactive-impulsive subtypes of ADHD a decade after the publication of DSM-IV are still scarce. Given that inattention is the hypothesized core ADHD symptom, it remains to be demonstrated that hyperactive-impulsive children who are not inattentive have the same condition. One of the main research deficits refers to data on treatment of the inattentive and hyperactive-impulsive subtypes.

Achievement↗
PubMed1993

Changes in the repertoire of peptides bound to HLA-B27 subtypes and to site-specific mutants inside and outside pocket B.

HLA-B27 subtypes share many structural features, including their pocket B, which interacts with a conserved Arg residue at the second position of B*2705-bound peptides. Subtypes differ among each other at other locations in the peptide binding site. In this study, metabolic labeling and radiochemical pool sequencing were used to address the following issues: (a) presence of the Arg 2 (R2) motif among peptides bound to the various HLA-B27 subtypes; (b) influence of mutations inside and outside pocket B on this motif; and (c) the degree of similarity among the peptide pools bound to the various B27 subtypes. Sequencing of Arg-labeled peptide pools extracted from B*2701 to B*2706, and from two site-directed mutants of B*2705 with changes outside pocket B, indicated that all of these molecules bind peptides with Arg at position 2. Peptides from several mutants with changes altering the structure of pocket B, and from one mutant at the pocket B rim, also retained the R2 motif. However, this was absent in the peptide pool extracted from the M45 mutant, in which the negative charge of pocket B, conferred to HLA-B27 by Glu45, was canceled. These results indicate that alterations outside pocket B, and even disruption of the network of hydrogen bonds that stabilizes Arg binding in pocket B, do not impair binding of peptides bearing the R2 motif, but a nonconservative substitution at position 45 does. As a substantial fraction of anti-B*2705 cytotoxic T lymphocyte (CTL) clones crossreact with the M45 mutant (Villadangos, J., B. Galocha, D. López, V. Calvo, and J. A. López de Castro. 1992. J. Immunol. 149:505) this result suggest that determinant mimicry by nonidentical peptides may frequently account for unexpected CTL crossreactions. Metabolic labeling with various other amino acids and radiochemical sequencing revealed similarities, but also substantial differences, among the peptide pools from the various HLA-B27 subtypes. This strongly suggests that many peptides bind to multiple subtypes, but significant subsets of peptides bound to a given HLA-B27 subtype do not bind to other subtypes or do so with greatly altered efficiency. These results indicate the importance of polymorphism outside pocket B in modulating peptide binding to HLA-B27.

Amino Acid Sequence↗
PubMed2000

Clinical implications of identifying non-B subtypes of human immunodeficiency virus type 1 infection.

Although human immunodeficiency virus type 1 (HIV-1) infection in the United States has predominantly involved subtype B, increasing global travel is leading to wider dissemination of genetically heterogeneous subtypes. While physicians depend on HIV-1 viral load measurements to guide antiretroviral therapy, commonly used molecular assays may underestimate the viral load of patients with non-B subtypes. Nine patients with non-B subtypes of HIV-1 were identified by physicians who suspected a non-B subtype on the basis of a low or undetectable HIV-1 viral load, by the Amplicor HIV-1 Monitor test, version 1.0, in conjunction with either a declining CD4 cell count or history of travel outside the United States. Use of version 1.5 of the Amplicor HIV-1 Monitor test detected a median HIV-1 viral load that was 2.0 log(10) RNA copies/mL higher than was determined with version 1.0. Clinical management was altered in all cases after diagnosis of a non-B-subtype infection. These cases demonstrate that it is critical for physicians to suspect and diagnose non-B subtypes of HIV-1 so that an assay with reliable subtype performance can be used to guide antiretroviral therapy.

Adult↗
PubMed2001

Human immunodeficiency virus type 1 reverse-transcriptase and protease subtypes: classification, amino acid mutation patterns, and prevalence in a northern California clinic-based population.

Phylogenetic analysis of the reverse transcriptase (RT) and protease of 117 published complete human immunodeficiency virus (HIV) type 1 genome sequences demonstrated that these genes cluster into distinct subtypes. There was a slightly higher proportion of informative sites in the RT (40.4%) than in the protease (34.8%; P= .03). Although most variation between subtypes was due to synonymous nucleotide substitutions, several subtype-specific amino acid patterns were observed. In the protease, the subtype-specific variants included 7 positions associated with drug resistance. Variants at positions 10, 20, 36, and 82 were more common in non-B isolates, whereas variants at positions 63, 77, and 93 were more common in subtype B isolates. In the RT, the subtype-specific mutations did not include positions associated with anti-retroviral drug resistance. RT and protease sequences from 2246 HIV-infected persons in northern California were also examined: 99.4% of the sequences clustered with subtype B, whereas 0.6% clustered with subtype A, C, or D.

Amino Acid Sequence↗
PubMed2002

Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda.

The effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression was investigated in 1045 adults in Uganda. At enrollment and every 6 months, a clinical history, examination, and laboratory investigations that included CD4 cell counts were done. HIV-1 envelope subtype was assessed mainly by peptide serology supplemented by heteroduplex mobility assay and DNA sequencing. A multivariate analysis of survival was performed to assess the prognostic value of HIV-1 subtype on death. A marginal general linear model also determined the effect of subtype on CD4 cell count during follow-up. Subtype D was associated with faster progression to death (relative risk, 1.29; 95% confidence interval, 1.07-1.56; P=.009) and with a lower CD4 cell count during follow-up (P=.001), compared with subtype A, after adjusting for CD4 cell count at enrollment. In Africa, envelope subtype D is associated with faster disease progression, compared with subtype A.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Evidence of two distinct subsubtypes within the HIV-1 subtype A radiation.

Members of HIV-1 group M are responsible for the vast majority of AIDS cases worldwide and have been classified on the basis of their phylogenetic relationships into nine roughly equidistant clades, termed subtypes. Although there are no known phenotypic correlates for these genotypes, the disproportionate spread of certain of these lineages has been taken to indicate that subtype-specific biological differences may exist. The subtype nomenclature thus remains an important molecular epidemiological tool with which to track the course of the group M pandemic. In this study, we have characterized HIV-1 strains described previously as unusual subtype A variants on the basis of partial sequence analysis. Six such strains from Cyprus (CY), South Korea (KR), and the Democratic Republic of Congo (CD) were PCR amplified from infected cell culture or patient PBMC DNA, cloned, and sequences in their entirety (94CY017, 97KR004, 97CDKTB48, and 97CDKP58) or as half genomes (97CDKS10 and 97CDKFE4). Distance and phylogenetic analyses showed that four of these viruses (94CY017, 97CDKTB48, 97CDKFE4, and 97CDKS10) were closely related to each other, but quite divergent from all other HIV-1 strains, except for subtype A viruses, which represented their closest relatives. In phylogenetic trees from gag, pol, env, and nef regions, the four newly characterized HIV-1 strains formed a distinct sister clade to subtype A, which was as closely related to subtype A as subsubtypes F1 and F2 are to each other. According to current nomenclature rules, this defines a subsubtype, which we have tentatively termed A2. The two other viruses, 97KR004 and 97CDKP58, as well as a full-length HIV-1 sequence from the sequence database (ZAM184), were found to represent complex A2/D, A2/G, and A2/C recombinants, respectively. These results indicate that HIV-1 subtype A is composed of two subsubtypes (A1 and A2), both of which appear to have a widespread geographic distribution. The A2 viruses described here represent the first reference reagents for this new group M lineage.

Cyprus↗
PubMed2002

Among 46 near full length HIV type 1 genome sequences from Rakai District, Uganda, subtype D and AD recombinants predominate.

The impact of HIV-1 genetic diversity on candidate vaccines is uncertain. To minimize genetic diversity in the evaluation of HIV-1 vaccines, vaccine products must be matched to the predominant subtype in a vaccine cohort. To that end, full genome sequencing was used to detect and characterize HIV-1 subtypes and recombinant strains from individuals in Rakai District, Uganda. DNA extracted from peripheral blood mononuclear cells (PMBC) was PCR amplified using primers in the long terminal repeats (LTRs) to generate nearly full length genomes. Amplicons were directly sequenced with dye terminators and automated sequencers. Sequences were phylogenetically analyzed and recombinants were detected and mapped with distance scan and bootscan. Among 46 sequences, 54% were subtype D, 15% were subtype A, and 30% were recombinant. All recombinants were individually unique, and most combined subtypes A and D. Subtype D comprised more than 70% of all the HIV-1 genomes in Rakai when both pure subtypes and recombinants were considered. Candidate vaccines based on HIV-1 subtype D would be appropriate for evaluation in Rakai District, Uganda.

Adolescent↗
PubMed2002

HIV type 1 subtypes circulating in eastern and northeastern regions of India.

Genetic subtyping has been a powerful tool in tracking the global spread of HIV. To determine the HIV-1 subtypes circulating in eastern and northeastern regions of India blood samples were collected from female sex workers in Calcutta and intravenous drug users (IDUs) in Manipur. Fifty-four samples from Calcutta and 25 samples from Manipur were analyzed for HIV-1 subtyping by heteroduplex mobility assay (HMA). Twenty-six samples from these regions were sequenced. HMA and sequencing of the samples from these regions revealed subtype C as the major subtype, circulating within both eastern and northeastern regions. In Manipur, subtype ThaiB was also detected as the second major subtype. Some of the IDUs from Manipur were found to be dual infected with subtype C and ThaiB.

Amino Acid Sequence↗
PubMed2003

Spreading of HIV-1 subtype G and envB/gagG recombinant strains among injecting drug users in Lisbon, Portugal.

We have evaluated the genetic diversity of HIV-1 strains infecting injecting drug users (IDUs) in Lisbon, Portugal. Heteroduplex mobility assay and/or phylogenetic analysis revealed that env (C2V3C3 or gp41) subtype B is present in 63.7% of the 135 viral samples studied, followed by subtypes G (23.7%), A (6.7%), F (5.2%), and D (0.7%). Similar analysis of gag (p24/p7) performed on 91 of the specimens demonstrated that 49.5% of the infections were caused by subtype G viruses; other gag subtypes identified were B (39.5%), F (3.3%), A and D (1.1.% each), and the recombinant circulating form CRF02_AG (5.5%). Discordant env/gag sub-types were detected in 34.1% of the strains and may reflect the presence of dual infections and/or recombinant viruses. The presumptive B/G recombinant form was highly predominant (21 of 31). The genetic pattern of HIV-1 subtype B and G strains is suggestive of multiple introductions and recombination episodes and of a longstanding presence of both subtypes in the country. C2V3C3 amino acid sequences from IDU-derived subtype G viruses presented highly significant signatures, which distinguish the variants from this transmission group. The unusually high prevalence of subtype G sequences (34.1%), independent of the geographic origin of the infected individuals, makes this IDU HIV-1 epidemic unique.

Adolescent↗
PubMed2003

Natural polymorphisms of protease in protease inhibitor-naive HIV-1 infected patients in Korea: a novel L63M in subtype B.

To establish a baseline for monitoring resistance mutation to protease inhibitors (PI), we determined protease(PR) sequences in peripheral blood mononuclear cells obtained from 43 PI-naive Korean HIV-1 infected patients. Interestingly, phylogenetic analysis revealed that 41 of the sequences belonged to subtype B, one belonged to subtype A, and one was unique, not clustering with any subtype. Thirty-one (76%) of the 41 sub-type B sequences formed a subclade within subtype B, a so-called "Korean B cluster." Polymorphisms were observed at 34 (34.3%) of the PR codons. One patient (2.3%) harbored a primary resistance-conferring mutation, L90M along with L63P and A71V, and all 43 strains showed some secondary associated with drug resistance. The percentage of patients with 7, 5, 4, 3, 2, and 1, resistance mutations were 2%, 2%, 14%, 23%,37%, and 9%, respectively. A novel polymorphism in subtype B, L63M was detected in two patients. Another patient showed a gross deletion (257 bp) after codon 91. The average genetic distance of the 41 subtype B sequences to the HXB2 sequence was 3.0% (range, 1.0-5.1%). Six hemophiliacs were infected with a domestic strain of HIV-1 subtype B, while the other two hemophiliacs were infected with nondomestic subtype B and had lived outside Korea. Although this is the first report on the molecular nature of PR in Korea, there is also a need to establish baselines for nonsubtype B HIV-1.

Adolescent↗