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PubMed2003

Irritable bowel syndrome subtypes according to bowel habit: revisiting the alternating subtype.

BACKGROUND: Disturbed bowel habit, diarrhoea or constipation is a key manifestation of irritable bowel syndrome (IBS). In some patients, diarrhoea and constipation alternate, giving rise to the so-called alternating subtype. AIMS: To assess IBS subtype breakdown (constipation (C-IBS), diarrhoea (D-IBS) or alternating (A-IBS)) according to the Rome II criteria and patients' self-assessment, the predominance in the alternating subtype (i.e. constipation, diarrhoea or neither), and the medical and personal impact, including health-related quality of life (HRQoL), of the different IBS subtypes. SUBJECTS AND METHODS: Two thousand individuals selected randomly to represent the general population were classified as potential IBS subjects (n = 281) or as non-potential IBS subjects (n = 1719) according to a validated questionnaire. Bowel habit classification was determined using the Rome II IBS supportive symptoms. RESULTS: Among 201 subjects meeting the Rome I criteria, 15% presented with D-IBS, 44% presented with C-IBS, 19% presented with A-IBS, and 22% presented with normal bowel habit. Among the 63 subjects meeting the Rome II criteria, 23% presented with A-IBS. According to the subjects' self-assessment, of those meeting the Rome I criteria, 16% considered themselves to have D-IBS, 66% to have C-IBS and 18% to have A-IBS. In subjects meeting the Rome II criteria, 24% considered themselves to have A-IBS. Among those classified with A-IBS by the Rome II criteria, most considered themselves to be constipated. Regardless of the subtype self-classification, most subjects reported a normal frequency of bowel movements. Clinical manifestations in A-IBS were very similar to those of C-IBS but with the added presence of defecatory urgency. Abdominal discomfort/pain and frequency of visits to physicians were greater in the A-IBS subtype than in the other two IBS subtypes. HRQoL was affected similarly in all IBS subtypes. CONCLUSIONS: Approximately one-quarter of subjects with IBS belong to the A-IBS subtype by the Rome II criteria, although the majority consider themselves to be constipated; indeed, clinical manifestations are more akin to the C-IBS subtype than to the D-IBS subtype. Abdominal discomfort/pain and frequency of visits to physicians are greater in the A-IBS subtype than in the other two IBS subtypes, while HRQoL is impaired similarly.

Adolescent↗

PubMed1992

Histone H1a subtype presents structural differences compared to other histone H1 subtypes. Evidence for a specific motif in the C-terminal domain.

Following a previous isolation by reverse-phase HPLC of five histone H1 subtypes from adult rat liver, purity of three of them, H1a, H1b and H1d (according to Lennox's nomenclature), was achieved. Structural features of these three subtypes were investigated. Partial cleavage of these subtypes by endoproteinase Glu-C showed a different behavior of the H1a subtype when compared to the H1b and H1d subtypes. Under the conditions used in this work, the H1b and H1d subtypes present three major sites accessible to the endoproteinase Glu-C, while the H1a subtype presents only one major site accessible to the proteinase. Partial N-terminal sequence of the different fragments obtained after proteolysis indicated that the two H1b and H1d subtypes were cleaved inside the globular domain (Glu-54,-75) and between the globular domain and the C-terminal one (Glu-116). The H1a subtype was only cleaved between the globular domain and the C-terminal tail (Glu-116), though Glu-54 and Glu-75 sites were present. These results would suggest some differences in the conformation of these proteins. Furthermore, the partial determined sequences of H1b and H1d showed 85% similarity to each other (the main differences were threonine residues instead of alanine residues in the C-terminal domain) while H1a was only 60% similar to H1b and H1d, for the sequences which aligned. The strongest differences between the H1a subtype and the two other subtypes were observed in the first amino acid residues of the C-terminal domain. The 117-126 amino acid residues (SKASTTKVTV) of H1a were quite different from those of H1b and H1d. This sequence, which showed a number of serine and threonine residues, was not found in any other histone sequence, after consultation with data bases. This H1a subtype was a minor component in adult liver (2.4%). As it was described in testis as a major component, testis histone H1 proteins were fractionated onto reverse-phase HPLC under the same conditions as those used for histone H1 proteins from liver. The pure testis H1a fraction was submitted to the endoproteinase Glu-C digestion. The pattern digestion was the same as that observed for liver H1a. The two 44-76 and 117-126 determined amino acid residues of H1a from testis were strictly identical to those of liver H1a. We demonstrate that H1a is the same protein in liver and testis and we give evidence for a specific motif SKASTTKVTV (117-126 residues) in the sequence of the C-terminal domain.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed2003

Differential prevalence of HIV type 1 subtype B and CRF01_AE among different sexual transmission groups in Tokyo, Japan, as revealed by subtype-specific PCR.

We determined the subtype of HIV-1 in 89 infected individuals attending three reference hospitals located in the Tokyo metropolitan area of Japan. Subtyping was performed with subtype-specific polymerase chain re-action (PCR) distinguishing subtype A, B, C, and CRF01_AE and/or phylogenetic analysis of HIV-1 env C2V3C3 sequences. Subtype-specific PCR provided unequivocal results in 97% of samples. Sixty-five subjects were infected with subtype B, 16 with CRFO1_AE, 4 with subtype A, 1 with CRF02_AG, and 3 with subtype C. Among 31 Japanese individuals infected through heterosexual contact, 13 were infected with subtype Band 12 with CRFO1_AE. All of the 41 Japanese men infected through homosexual contact harbored subtype B. These results indicate that subtype B is exclusively predominant in a homosexually transmitted group, whereas subtype B and CRFO1_AE are evenly predominant in a heterosexually transmitted group.

Female↗

PubMed2003

Patterns of point mutations associated with antiretroviral drug treatment failure in CRF01_AE (subtype E) infection differ from subtype B infection.

An increasing number of HIV-1-infected patients living in developing countries now have access to antiretroviral drugs. Information regarding the drug-resistant mutations of non-B subtype HIV-1 remains limited, however. The authors cross-sectionally compared patterns of the drug-resistant point mutations in patients infected with either subtype B or CRF01_AE (subtype E) among patients who acquired HIV by sexual transmission in Japan. Protease sequence data were available from 216 patients with a detectable level of RNA copies in plasma. Based on phylogenetic analysis of the protease and the C2V3 regions, 162 subtype B and 45 CRF01_AE cases were identified; 82 subtype B and 24 CRF01_AE patients had a treatment failure with nucleoside reverse transcriptase inhibitors; and 69 subtype B and 19 CRF01_AE patients had a treatment failure with a protease inhibitor. Antiretroviral drug history was similar in subtype B-infected and CRF01_AE-infected patients. The mutations T69N and V75M in reverse transcriptase and L10F, K20I, L33I, and N88S in protease were seen more frequently in patients infected with CRF01_AE than in patients with subtype B. The mutations, D30N, A71V, and N88D were found exclusively in patients with subtype B. Most of the characteristic mutation patterns were associated with a history of receiving nelfinavir. The pattern of drug resistance mutations differs between the subtypes. Data derived from subtype B drug-resistant genotypes may not always be applicable to non-B subtypes.

Adult↗

PubMed2006

Subtype I BK polyomavirus strains grow more efficiently in human renal epithelial cells than subtype IV strains.

BK polyomavirus (BKPyV) is ubiquitous in human populations, infecting children without obvious symptoms and persisting in the kidney. BKPyV isolates have been classified into four subtypes (I-IV) using either serological or genotyping methods. In general, subtype I occurs most frequently, followed by subtype IV, with subtypes II and III rarely detected. As differences in growth capacity in human cells possibly determine the proportion of the four subtypes of BKPyV in human populations, here the growth properties of representative BKPyV strains classified as subtype I or IV in renal proximal tubule epithelial cells (HPTE cells) of human origin were analysed. HPTE cells were transfected with four and three full-length BKPyV DNAs belonging to subtypes I and IV, respectively, and cultivated in growth medium. Virus replication, detected using the haemagglutination assay, was observed in all HPTE cells transfected with subtype I BKPyV DNAs, whereas it was markedly delayed or not detected in those transfected with subtype IV BKPyV DNAs. It was confirmed that the transfected viral DNAs induced virus replication in HPTE cells. Furthermore, it was found that BKPyVs with archetypal transcriptional control regions replicated in HPTE cells, with only the occasional emergence of variants carrying rearranged transcriptional control regions. Essentially the same results as described above were obtained with renal epithelial cells derived from whole kidney. Thus, it was concluded that subtype I BKPyV replicates more efficiently than subtype IV BKPyV in human renal epithelial cells, supporting the hypothesis that growth capacity in human cells is related to the proportion of BKPyV subtypes in human populations.

BK Virus↗

PubMed1987

Point mutation in the S gene of hepatitis B virus for a d/y or w/r subtypic change in two blood donors carrying a surface antigen of compound subtype adyr or adwr.

Genomes of hepatitis B virus (HBV) were cloned from the plasma of a blood donor who carried subviral particles of three distinct subtypes in the following proportions: adr, 25%; ayr, 63%; and adyr, 12%. HBV DNA clones were classified into two groups based on a difference at only one nucleotide in the S gene. Two clones had A as nucleotide 365 that formed part of the codon for lysine as amino acid residue 122 and produced a surface antigen of subtype adr in transfected NIH 3T3 cells. The remaining four clones had G determining the codon for arginine and produced a surface antigen of subtype ayr in transfected cells. Similarly, HBV genomes were cloned from the plasma of an individual who carried subviral particles of subtypes adr (71%) and adwr (29%). Two clones had T and A as nucleotides 476 and 479, respectively. The other seven clones had C and G as the respective nucleotides. Based on a comparison with previously reported HBV genomes of various subtypes, the mutation of nucleotide 479, forming part of the codon for lysine or arginine as amino acid residue 160, was deduced to determine the w or r subtype, respectively. When NIH 3T3 cells were transfected separately with the genome of subtype adw or adr, derived from plasma containing a surface antigen of subtype adwr, and then cocultured, they produced subviral particles of either subtype adw or adr. When cells were transfected with the genomes of subtypes adw and adr simultaneously, however, subviral particles were produced that possessed w and r determinants on the selfsame particles. These results attributed the d/y or w/r subtypic change to a point mutation in the S gene and favored coinfection of hepatocytes with an HBV genome and its mutant as the mechanism of compound subtypes.

Base Sequence↗

PubMed1997

pol gene diversity of five human immunodeficiency virus type 1 subtypes: evidence for naturally occurring mutations that contribute to drug resistance, limited recombination patterns, and common ancestry for subtypes B and D.

Naturally occurring mutations in the polymerase gene of human immunodeficiency virus type 1 (HIV-1) have important implications for therapy and the outcome of clinical studies. Using 42 virus isolates obtained from the UNAIDS sample collection, we analyzed the protease (99 amino acids [aa]) and the first 297 aa of reverse transcriptase (RT) coding regions. Based on the V3 sequence analysis, the collection includes subtype A (n = 5), subtype B (n = 12), subtype C (n = 1), subtype D (n = 11), and subtype E (n = 13) viruses. Of the 42 protease genes, 37 contained naturally occurring mutations at positions in the gene that contribute to resistance to protease inhibitors (indinavir, saquinavir, ritonavir, and nelfinavir) in clade B isolates. The phenotypic effect of these substitutions in non-B isolates is unclear. The The 5'half RT coding region of the 42 isolates was found to be less variable, although 19 of the 42 RT sequences contained amino acid substitutions known to contribute to nucleoside and/or nonnucleoside drug resistance. Since the virus isolates were obtained in 1992, it is unlikely that the infected subjects received protease inhibitors, but we found evidence that one subject acquired a zidovudine (AZT)-resistant HIV-1 strain from a contact who had received AZT. Phylogenetic analysis identified five subtype pol clusters: A, B, C, D, and A'. Comparison of env and pol sequences of the same viruses showed no more recombination events than were already identified on the basis of gag/env comparison (M. Cornelissen, G. Kampinga, F. Zorgdrager, J. Goudsmit, and the UNAIDS Network for HIV Isolation and Characterization, J. Virol. 70:8209-8212, 1996). In one of the known recombinants, a crossover site between subtypes A and C could be identified, and in another, a crossover site could not be identified due to lack of a reference subtype F pol sequence. We analyzed the ds/da ratio of gag, pol, and env sequences of 35 isolates, excluding the recombinants. Our analysis showed that gag and pol are subjected to purifying selection with an average ds/da ratio above 1, independent of the subtype and in contrast with V3 (ds/da approximately 1). Based on the low ds/da ratio of the intergroup analysis of A/E and B/D gag and pol sequences, we analyzed the evolutionary relation between subtypes B and D in more detail by constructing separate phylogenetic trees for synonymous and nonsynonymous substitutions. Our analysis suggests a common ancestry for subtypes B and D that is distinct from that of subtypes A and E.

Amino Acid Sequence↗

PubMed2026

Immune subtyping of colorectal adenoma identifies a subtype with activated adaptive immunity ahead of progressing to cancer.

BACKGROUND: Colorectal adenomas (CRA) represent precursor lesions with varying risks of malignant transformation. However, molecular subtyping, particularly immune-related classification, remains underexplored in adenomas. This study aims to characterize the immune landscape of CRA through immune subtyping and evaluate its association with cancer progression, gene expression signatures, and functional pathways. METHODS: We conducted a retrospective analysis of transcriptomic data from multiple cohorts of CRA samples. Immune subtypes were identified using non-negative matrix factorization (NMF) based on immune-related genes. Diverse deconvolution algorithms were used to estimate immune cell infiltration. The immune status alteration in premalignant lesion was further consolidated by single-cell transcriptome data. Differential gene expression analysis was performed between subtypes, followed by functional enrichment analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]). RESULTS: Two distinct immune subtypes were identified: an immune-enriched subtype characterized by high lymphocyte infiltration and elevated expression of immune-related genes, and an immune-deficient subtype with suppressed immune activity. Differential expression analysis revealed significant upregulation of immune response genes (e.g., CD4, CD86, HLA-DRA) in the immune-enriched subtype. GO and KEGG analyses highlighted enrichments in leukocyte transendothelial migration, chemokine signaling, and antigen processing and presentation pathways. Single-cell result revealed an early occurrence of TIGIT activation and exhausted CD8 T cell features in adenoma when compared to normal tissue. CONCLUSION: This study delineates distinct immune subtypes within CRAs. The immune-enriched subtype demonstrates activated adaptive immunity and may reflect a higher potential for immune surveillance, while the immune-deficient subtype exhibits stromal features suggestive of progressive transformation. These findings provide insights into early immune microenvironment alterations and may inform strategies for risk stratification and immunoprevention in colorectal carcinogenesis.

Colorectal adenoma↗

PubMed1999

Genetic analysis of human immunodeficiency virus in Abidjan, Ivory Coast reveals predominance of HIV type 1 subtype A and introduction of subtype G.

To better understand the molecular epidemiology of HIV genetic diversity in Abidjan, Ivory Coast, we performed a genetic analysis of 170 HIV-1-seropositive specimens representing newly diagnosed tuberculosis patients (n = 143) and women monitored in a mother-to-child transmission cohort study (n = 27). Preliminary screening with RFLP presumptively classified 162 (95.3%) of these as subtype A. The envelope region of 108 specimens was subtyped by sequence analysis: 102 (94.4%) were subtype A, 2 (1.9%) were subtype D, and 4 (3.7%) were subtype G. Subtyping gag and env regions of the genome suggested that five of the six nonsubtype A isolates exhibited a potentially mosaic structure. A comparative phylogenetic analysis of HIV-1 subtype A C2V3 from 27 Ivory Coast and 21 Ugandan sequences revealed a striking clustering among Ivory Coast variants, and an independent segregation from Ugandan subtype A. Despite independent clustering with other subtype A specimens, limited variability of the V3 loop apex was observed; the globally predominant V3 motif, GPGQ, represented 90.1% of the HIV-1 strains. This study demonstrates that clade A is the predominant HIV-1 subtype in HIV-seropositive individuals in Abidjan, Ivory Coast and that these strains are phylogenetically distinct from other subtype A strains observed in East Africa.

Amino Acid Sequence↗

PubMed2005

No evidence for rapid subtype C spread within an epidemic in which multiple subtypes and intersubtype recombinants circulate.

There are multiple subtypes of HIV-1 circulating worldwide, but recently, subtype C has become highly prevalent, particularly in certain geographic regions. It is unclear whether the dominance of subtype C or other subtypes is due to increased fitness of certain subtypes for transmission, or a founder effect in new, rapidly growing epidemics. To examine whether the prevalence of one subtype increases over the course of an expanding epidemic that includes several circulating subtypes, we examined the distribution of HIV-1 subtypes in Kenya from 1986 to 2000. We found no evidence for an increase in the prevalence of subtype C, which remained low throughout this approximately 15-year period. Interestingly, the percentage of subtype D present in the population decreased significantly over that period, with a slight increase in subtype A. Throughout that period, intersubtype recombinant viruses were detected, including at the early stages of the epidemic. This latter finding suggests that reinfection may have occurred in high-risk groups early in the epidemic, leading to intersubtype recombinant viruses that underwent secondary spread.

Adolescent↗

PubMed2007

In a mixed subtype epidemic, the HIV-1 Gag-specific T-cell response is biased towards the infecting subtype.

OBJECTIVES: Southwest Tanzania is affected by an HIV-1 epidemic consisting of subtypes A, C, and D, and their recombinant forms. This study was designed to assess whether the Gag- and Nef-specific T-cell response is biased towards recognizing the infecting subtype. METHODS: The infecting subtypes were characterized with a Multi-hybridization assay that discriminates between subtypes A, C and D. The interferon-gamma ELISPOT assay was used to detect the Gag- and Nef-specific T-cell responses in freshly isolated peripheral blood mononuclear cells in 56 seropositive patients. To study the HIV-specific T-cell responses, isolate-based Gag and Nef peptide sets representative of the locally occurring subtypes were used. The results were analysed at the total protein and single peptide level. RESULTS: In the study population, 35% were infected with a pure C subtype, 24% and 23% with ACD or AC recombinant forms, respectively. The total magnitude (P < 0.01) and breadth (P < 0.01) of the Gag-specific T-cell response detected with the subtype C-Gag peptide set was significantly greater than that detected with either the subtype A-Gag or D-Gag peptide sets. No significant difference was observed in the Nef-specific response. In 85% of responses targeting the most immunodominant Gag epitopes with subtype-specific sequence differences, the best recognized epitope variant corresponded to the infecting subtype. CONCLUSIONS: The Gag-specific T-cell response had a preference for recognizing peptides related to the infecting subtype.

Amino Acid Sequence↗

PubMed2002

Human immunodeficiency virus type 1 subtype C exhibits higher transactivation activity of Tat than subtypes B and E.

Although human immunodeficiency virus type 1 (HIV-1) subtypes C and E are expanding faster and seem to be of greater global significance than HIV-1 subtype B, there is only little information about Tat activity of such non-B subtypes. Here, we showed evidence that subtype C Tat exhibits higher transcriptional activity from the HIV-1 long-terminal repeat (LTR) in a human T-cell line, compared with subtypes B and E. This higher activity of subtype C Tat was not due to the LTR, but to the Tat sequence variability. We examined three candidate regions with sequence for the higher activity of subtype C Tat, such as the cysteine-rich motif, the basic domain, and the 2nd exon. The results showed that the variation in subtype C Tat at two amino acid residues, Ser57 and Glu63 in stead of Arg57 and Gln63 in subtypes B and E, within and close to the basic domain were involved in the higher activity of subtype C Tat. This variation did not affect its nuclear localization activity. Thus, there may be a significant advantage for the high Tat activity on subtype C replication.

Amino Acid Sequence↗

PubMed2006

Validation of population-based ADHD subtypes and identification of three clinically impaired subtypes.

Statistically based classification methods have successfully refined ADHD into homogenous and heritable subtypes. External validity and impairment of these subtypes was examined using the Child Behavior Checklist (CBCL). We compared mean CBCL syndrome and competency t-scores across ADHD subtypes defined by latent class analysis in a sample of 1,346 individual twins from Missouri. The potential for comorbidity with conduct disorder (CD), oppositional defiant disorder (ODD), or major depression (MD) to increase impairment in specific ADHD subtypes was also examined. CBCL profiles confirm differences in severity, with more severe classes having increased syndrome scale and decreased competency scale CBCL scores. Clinically significant impairment was found for severe inattentive and combined subtypes and the mild combined subtype. Overall, the presence of comorbid CD, ODD, or MD did not result in increased ADHD subtype impairment. CBCL scores distinguish impairment in ADHD subtypes created through LCA. Comorbidity with CD, ODD, or MD does not significantly increase impairment among ADHD subtypes. The mild combined ADHD subtype represents a clinically significant but under-studied form of ADHD.

Adolescent↗

PubMed2004

Measurement of HIV RNA in patients infected by subtype C by assays optimized for subtype B results in an underestimation of the viral load.

Quantitation assays of HIV-1 RNA used currently were designed and optimized for subtype B viruses. However, infection with non-B HIV viruses has become more common worldwide. Unfortunately, little information is available regarding the suitability of these assays for measurement of viral load in specific non-B subtypes. The performance of two commercial HIV-1 RNA quantitation assays was evaluated in 82 HIV subtype C-infected patients and in 43 HIV-1 subtype B-infected patients. Blood samples were tested by the Amplicor HIV-1 Monitor Assay, Version 1.5, and by the nucleic acid sequence-based amplification HIV-1 assay (NucliSens). The results were compared by using a paired, two-tailed Student's t-test; the difference between the assays was found to be significant only for subtype C. Discordant results (>0.5 log difference) between the two assays were detected in 39% of subtype C samples, compared to 23.2% of subtype B samples. In all cases in which a discordant result was detected, the lower results were obtained by the NucliSens assay. Discordant results between CD4 and viral load (CD4 < 200 cells/ml with a viral load <5,000 copies/ml) were observed in eight of the subtype C-infected patients when a viral load was measured by NucliSens (9.7%), compared to three patients (3.6%) when measured by the Amplicor assay. In conclusion, in patients with HIV subtype C infection, measurement of HIV RNA by the NucliSens assay resulted in a significant underestimation of the viral load as compared to the Amplicor assay. As a consequence, such an underestimation may result in sub-optimal care of patients infected with HIV subtype C.

CD4 Lymphocyte Count↗

PubMed1994

Oligotyping of HLA-A2, -A3, and -B44 subtypes. Detection of subtype incompatibilities between patients and their serologically matched unrelated bone marrow donors.

We have set up a simple PCR-SSO oligotyping procedure that is able to discriminate ten HLA-A2 (2 PCR/11 probes), two HLA-A3 (1 PCR/1 probe), and two HLA-B44 subtypes (1 PCR/2 probes). The frequency of these subtypes has been determined in a large panel of local blood donors and leukemic patients in combination with their unrelated potential donors. A*0201 and A*0301 were the predominant subtypes (> 95%) for A2 and A3, respectively. B*4402 occurred twice as frequently as B*4403. A2 and B44 subtype mismatches were analyzed in a group of 30 patients and their 116 unrelated potential donors who were matched serologically (low-stringency matching: AB without splits, DR1-10). For seven patients (23%) at least one A2- or B44-subtype-mismatched donor was found. For two of these patients (7%), the subtype-mismatched donor would have been considered as compatible on the basis of high stringency matching (AB splits, DRB1 subtypes, DRB3/B5). For one patient of Mediterranean origin, all five donors recruited from a north European registry (matched with high stringency) appeared to be subtype incompatible (A*0201/A*0205). The rather low percentage of A2- and B4-subtype mismatches in DRB1/B3/B5 matched combinations confirms the significance of linkage disequilibria of HLA antigens. Because unrelated donor selection is done through international registries, however, class I subtyping might be necessary when individuals originate from different geographic areas.

Base Sequence↗

PubMed2000

Near-full-length genome sequencing of divergent African HIV type 1 subtype F viruses leads to the identification of a new HIV type 1 subtype designated K.

We recently reported a high divergence among African subtype F strains. Three well-separated groups (F1, F2, and F3) have been shown based on the phylogenetic analysis of the p24 gag and envelope sequences with genetic distances similar to those observed for known subtypes. In this study, we characterized the near-full-length genomes of two strains from epidemiological unlinked individual belonging to each of the subgroups: F1 (96FR-MP411), F2 (95CM-MP255 and 95CM-MP257), and F3 (96CM-MP535 and 97ZR-EQTB11). Phylogenetic analysis of the near-full-length sequences and for each of the genes separately showed the same three groups, supported by high bootstrap values. Diversity plotting, BLAST subtyping, and bootstrap plotting confirmed that the divergent F strains correspond to nonrecombinant viruses. The divergence between F1 and F2 is consistently lower than that seen in any other intersubtype comparison, with the exception of subtypes B and D. Based on all the different analyses, we propose to divide subtype F into two subclades, with F1 gathering the known subtype F strains from Brazil and Finland, and our African strain (96FR-MP411), and F2 containing the 95CM-MP255 and 95CM-MP257 strains from Cameroon. The F3 strains, 97ZR-EQTB11 from the Democratic Republic of Congo and 96CM-MP535 from Cameroon, meet the criteria of a new subtype designated as K. The equidistance of subtype K to the other subtypes of HIV-1 suggests that this subtype existed as long as the others, the lower distance between B and D, and between F1 and F2 suggest a more recent subdivision for these latter strains.

Africa↗

PubMed1998

Molecular epidemiology of HIV-1 in Brazil: high prevalence of HIV-1 subtype B and identification of an HIV-1 subtype D infection in the city of Rio de Janeiro, Brazil. Evandro Chagas Hospital AIDS Clinical Research Group.

HIV-1-positive individuals were recruited from January 1993 to December 1996 from several cohorts receiving follow-up in the city of Rio de Janeiro, Brazil, to evaluate HIV-1 genetic variability and the potential association with modes of transmission. HIV-1 subtyping was carried out using the heteroduplex mobility assay (HMA), and those samples corresponding to the typical Brazilian subtype B variant were further identified based on the Fok I restriction fragment length polymorphism (RFLP). DNA sequencing was performed to evaluate one case of subtype D infection. From the 131 HIV-1-positive individuals analyzed, 106 (80.9%) could be identified as infected by subtype B and 20 (15.3%) by subtype F. One of the samples (0.8%) was classified as subtype D. DNA samples from 4 patients (3.0%) did not yield polymerase chain reaction (PCR)-amplified products to be typed. Based on the Fok I RFLP, 39 of the 106 subtype B samples (37%) were identified as corresponding to the typical Brazilian subtype B variant containing the GWGR motif at the tip of the V3 loop. No statistically significant association could be detected between HIV-I subtypes and modes of transmission, exposure categories, or gender. This is the first reported case of HIV-1 subtype D infection in Brazil.

Amino Acid Sequence↗

PubMed2006

An adenovirus-based HIV subtype B prime/boost vaccine regimen elicits antibodies mediating broad antibody-dependent cellular cytotoxicity against non-subtype B HIV strains.

Although HIV subtype B predominates in North America and Western Europe, most HIV infections worldwide are non-subtype B. Globally effective AIDS vaccines need to elicit broad immunity against multiple HIV strains. In this study, 10 chimpanzees were intranasally primed sequentially with adenovirus type 5 (Ad5)- and Ad7-HIVMNenv/rev recombinants and boosted twice intramuscularly with heterologous oligomeric HIVSF162 gp140DeltaV2 protein in MF59 adjuvant. Sera were evaluated for binding, neutralizing, and antibody-dependent cellular cytotoxicity (ADCC) against HIV clades A, B, C, and CRF01_AE. The vaccine regimen elicited high-titered HIV subtype A, B, C and CRF01_AE gp120-binding antibodies. Sera from 7 of 10 vaccinated chimpanzees cross-neutralized the heterologous South African subtype C primary HIVTV-1 isolate. Significant cross-clade neutralization against other subtype A, C and E isolates was not observed. Sera from all animals mediated ADCC of cells coated with gp120 from HIV subtypes A and B. Nine of 10 animals also exhibited ADCC activity against HIV subtype C and CRF01_AE gp120-coated targets. This subtype B Ad-HIV recombinant prime/envelope protein boost regimen is a promising approach for eliciting broad ADCC activity against diverse HIV clades. Incorporating additional non-subtype B envelope genes and protein boosts in a multivalent strategy may be required to elicit broader neutralizing antibodies against non-subtype B HIV strains.

AIDS Vaccines↗