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PubMed2005

Replication of subtypes for smoking cessation within the contemplation stage of change.

OBJECTIVE: Tailored interventions based on stage of change and other Transtheoretical Model constructs have been effective for promoting smoking cessation. Recent cluster analyses based on the Pros and Cons from the Decisional Balance and the Situational Temptations measures performed within the stages have suggested the existence of distinct cluster subtypes. Cluster subtypes would permit the development of tailored interventions focusing on these subtypes. This study attempts to replicate cluster subtypes within the Contemplation stage of change in a secondary analysis of data from a sample of current smokers (N=3967). METHOD: Four random samples of 400 were selected from the 1734 Contemplators. The cluster analyses were performed using the Pros, Cons, and Situational Temptations. Interpretability of the pattern, pseudo-F-test, and dendograms were used to determine the number of clusters. RESULTS: Four distinct cluster subtypes (Classic Contemplators, Progressing, Early Contemplators, and Disengaged) were found and replicated across samples. The clusters were externally validated using the 10 Processes of change and 2 smoking behavior variables (cigarettes per day and time before first morning cigarette). Statistically significant (p<0.05) multivariate effects were found for the 10 Processes of change in all four samples. The cluster groups differed on 7 or more of the processes in each sample. Significant multivariate effects were also found for the smoking behavior variables in all samples (p<0.001). CONCLUSIONS: The cluster patterns closely replicate earlier findings and provide evidence for the existence of clusters subtypes within the Contemplation stage of change.

Adolescent↗

PubMed2005

Replication of subtypes for smoking cessation within the Preparation stage of change.

OBJECTIVE: Recent cluster analyses based on the Pros and Cons and the Situational Temptations measures performed within the stages of change defined by the Transtheoretical Model have suggested the existence of distinct cluster subtypes. The goal of this study is to replicate cluster subtypes within the Preparation stage of change in a secondary analysis of data from a sample of current smokers (N=3967). Identification of stable cluster subtypes would permit the development of tailored interventions focusing on these subtypes. METHOD: Two random samples of approximately 340 subjects were selected from the 686 participants in the Preparation stage. The cluster analyses were performed using the Pros, Cons and Situational Temptations. Interpretability of the pattern, pseudo F test, and dendograms were used to determine the number of clusters. RESULTS: Four distinct cluster subtypes (Classic, Progressing, Early Preparation, and Disengaged) were found and replicated across samples. The clusters were externally validated using the ten processes of change and two smoking behavior variables. Statistically significant (p<0.05) multivariate effects were found for the ten processes of change and the smoking behavior variables (p<0.001) in the two samples. CONCLUSIONS: The cluster patterns replicate earlier findings and provide evidence for the existence of clusters subtypes within the Preparation stage of change.

Adaptation, Psychological↗

PubMed2006

Signal transduction and regulation: are all alpha1-adrenergic receptor subtypes created equal?

The current manuscript reviews the evidence whether and how subtypes of alpha(1)-adrenergic receptors, i.e. alpha(1A)-, alpha(1B)- and alpha(1D)-adrenergic receptors, differentially couple to signal transduction pathways and exhibit differential susceptibility to regulation. In both regards studies in tissues or cells natively expressing the subtypes are hampered because the relative expression of the subtypes is poorly controlled and the observed effects may be cell-type specific. An alternative approach, i.e. transfection of multiple subtypes into the same host cell line overcomes this limitation, but it often remains unclear whether results in such artificial systems are representative for the physiological situation. The overall evidence suggests that indeed subtype-intrinsic and cell type-specific factors interact to direct alpha(1)-adrenergic receptor signaling and regulation. This may explain why so many apparently controversial findings have been reported from various tissues and cells. One of the few consistent themes is that alpha(1D)-adrenergic receptors signal less effectively upon agonist stimulation than the other subtypes, most likely because they exhibit spontaneous internalization.

Animals↗

PubMed2006

Immunohistochemical localization of dopamine receptor subtypes (D1R-D5R) in Alzheimer's disease brain.

Among the neurotransmitter abnormalities that have been investigated in Alzheimer's disease (AD), deficits in the cholinergic system have been the most intensively studied. Another key neurotransmitter system involved with emotion and cognition is the dopaminergic system. Here we have investigated alterations in all five dopamine receptor subtypes in AD brain. Using antipeptide rabbit antibodies for each of the five dopamine receptors (D1-D5) we mapped the distribution of these receptors in postmortem AD and age-matched control brains in the frontal cortex, utilizing biotin-avidin immunocytochemistry. All five DR subtypes were expressed as cell surface and cytoplasmic proteins. Receptor-specific changes in control and AD brain were identified as follows: D4R and D3R were the predominant receptor subtypes in age-matched controls followed by D2R and D1R; D5R is the least expressed receptor subtype. In AD brain, D2R and D5R are well expressed in comparison to D1R, D3R and D4R. Expression of D1R, D3R and D4R was severely reduced in AD cortex. D2R expression is moderately reduced in the frontal cortex of AD brain. D5R is the only receptor subtype whose expression is increased in AD frontal cortex. Furthermore, in AD, we found comparable expression of D3R in astrocytes, whereas D5R-like immunoreactivity is significantly increased in astrocytes, in comparison to normal frontal cortex, where it was predominantly neuronal. These results demonstrate subtype-specific changes in dopamine receptors in AD that may be important in disease pathophysiology and that may also serve as potential targets for therapeutic intervention in AD.

Aged↗

PubMed2004

V-val subtype of Epstein-Barr virus nuclear antigen 1 preferentially exists in biopsies of nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) has been suggested to be involved in pathogenesis of nasopharyngeal carcinoma (NPC). However, EBV infection is ubiquitous, whereas NPC occurs with strong geographic and racial distribution. Whether a substrain of EBV contributes to this phenomenon remains uncertain. Epstein-Barr virus nuclear antigen 1 (EBNA-1) is one of the most frequently detected EBV proteins in NPC tissues. Based on the polymorphism of amino acids at position 487, EBNA-1 is classified into five subtypes: P-ala, P-thr, V-val, V-leu and V-pro. To examine the relationship between subtypes of EBNA-1 and NPC, we determined the subtypes of EBNA-1 in biopsies of NPC, peripheral blood lymphocytes (PBL), and throat washings (TWs) obtained in endemic and non-endemic areas of NPC within China. The results revealed that V-val was the only subtype detected in NPC tissue, whereas three subtypes of EBNA-1, V-val, P-ala, and P-thr, were detected in PBL and TWs irrespective of origin, and mixed infection of V-val and P-ala was also observed. In addition, the variations of V-val derived from biopsies of NPC were identical to those derived from PBL and TWs in the context of N-terminus and C-terminus of EBNA-1. These facts indicate that a substrain of EBV with V-val subtype of EBNA-1 infects NPC preferentially and a susceptibility to a particular EBV isolate in the nasopharynx may exist during development of NPC.

Base Sequence↗

PubMed2006

The proconvulsant effects of the GABAA alpha5 subtype-selective compound RY-080 may not be alpha5-mediated.

RY-080 (ethyl 8-ethynyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate) is an imidazobenzodiazepine with 40-50-fold higher affinity for the benzodiazepine binding site of alpha5- rather than alpha1-, alpha2- or alpha3-containing GABAA receptors. Previous data describing RY-080 as being convulsant suggests that inverse agonists selective for the alpha5 subtype may not be suitable for clinical development. In the present study, we show that RY-080 possesses inverse agonism for the alpha1 and alpha5 subtypes of human recombinant GABAA receptors and whilst not convulsant it was proconvulsant. Hence, with pentylenetetrazole alone, the dose predicted to give tonic convulsions in 50% of the mice (ED50) was 108 mg/kg whereas in the presence of 1 and 10 mg/kg RY-080, the ED50s were 93 and 57 mg/kg, respectively. In vivo [3H]L-655,708 and [3H]Ro 15-1788 binding assays showed that the subtype selectivity of RY-080 in vivo was 7-10-fold for alpha5-relative to alpha1- and alpha2/alpha3-containing receptors (respective ID50 values of 0.93, 9.7 and 6.2 mg/kg) and is therefore much lower than seen in vitro. Consequently, it is not possible to define a dose of RY-080 which gives high occupancy of the alpha5 subtype without binding to other subtypes and accordingly the proconvulsant effects of RY-080 cannot be attributed solely to the alpha5 subtype.

Alkynes↗

PubMed2006

Evaluation of the role of nicotinic acetylcholine receptor subtypes and cannabinoid system in the discriminative stimulus effects of nicotine in rats.

Male Wistar rats were trained to discriminate (-)-nicotine (0.4 mg/kg) from saline under a two-lever, fixed-ratio 10 schedule of water reinforcement. During test sessions the following drugs were coadministered with saline (substitution studies) or nicotine (0.025-0.4 mg/kg; combination studies): the alpha4beta2 nicotinic acetylcholine receptor subtype antagonist dihydro-beta-erythroidine (DHbetaE), the non-selective nicotinic acetylcholine receptor subtype antagonist mecamylamine, the alpha7 nicotinic acetylcholine receptor subtype antagonist methyllycaconitine (MLA), the alpha4beta2 nicotinic acetylcholine receptor subtype agonist 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-IA), the cannabinoid CB1 receptor antagonist/partial agonist rimonabant, the cannabinoid CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethylbicyclo-[2.2.1]heptan-2-yl]5-(4-chloro-3-methyl-phenyl)-1-(4-methybenzyl)pyrazole-3-carboxamide (SR 144528), the cannabinoid CB1/2 receptor agonists (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)-phenyl]-trans-4-(3-hydroxy-propyl)cyclohexanol (CP 55,940) or R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]-pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl)-methanone mesylate (WIN 55,212-2), the endogenous cannabinoid agonist and non-competitive alpha7 nicotinic acetylcholine receptor subtype antagonist anandamide, the anandamide uptake and fatty acid amide hydrolase inhibitor N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (AM-404), the fatty acid amide hydrolase inhibitor cyclohexylcarbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB 597), AM-404+anandamide or URB 597+anandamide. 5-IA (0.01 mg/kg) fully substituted for nicotine, while other drugs were inactive. In combination studies, DHbetaE and mecamylamine dose-dependently attenuated the discriminative stimulus effects of nicotine and the full substitution of 5-IA, while MLA, rimonabant, SR 144528, CP 55,940, WIN 55,212-2, and URB 597 did not alter the nicotine cue. Pretreatment with AM-404+anandamide or URB 597+anandamide weakly enhanced nicotine-lever responding. Our pharmacological analyses demonstrates that the expression of nicotine discrimination is under the control of nicotinic acetylcholine receptor subtypes composed of alpha4beta2 (but not of alpha7) subunits. Furthermore, we excluded the involvement of either cannabinoid CB1 and CB2 receptors or increases in the endocannabinoid tone in the nicotine discrimination.

Aconitine↗

PubMed2006

Prevalent HBV genotypes and subtypes in a South Indian population.

BACKGROUND: Genotypes or genetic subtypes describe genetically related strains and have been described for viruses belonging to several different families. The eight major genotypes of hepatitis B virus (HBV) have distinct geographic distribution. Recent studies suggest possible pathogenic and therapeutic differences among HBV genotypes. OBJECTIVES: To evaluate the HBV genotypes of 85 samples by RFLP analysis and sequence the desired region to look for variations and identify the subtypes of the surface region. STUDY DESIGN: We studied 85 patients with HBV in order to identify the most prevalent genotype and subtype. Patients with HBV-related liver disease attending the Department of Gastroenterology at Owaisi Hospital and Research Centre were studied. RESULTS AND CONCLUSIONS: Genotype D1 was most prevalent. Genotyping was carried out by RFLP analysis and confirmed by sequencing. Nucleotide sequences showed significant homology (96-97%) with the other genotypes that have been reported. Subtype ayw was the most prevalent subtype within the surface region. Construction of a phylogenetic tree incorporating these isolates and other published HBV sequences showed that the isolates are derived from the same evolutionary tree. The study adds to our understanding of the genetic diversity of HBV and the geographical distribution of its subtypes, and will be useful for reconstructing the evolutionary history of HBV.

Adult↗

PubMed2005

Thermodynamic and structural equivalence of two HLA-B27 subtypes complexed with a self-peptide.

The F pocket of major histocompatibility complex (in humans HLA) class I molecules accommodates the C terminus of the bound peptide. Residues forming this pocket exhibit considerable polymorphism, and a single difference (Asp116 in HLA-B*2705 and His116 in HLA-B*2709 heavy chains) confers differential association of these two HLA-B27 subtypes to the autoimmune disease ankylosing spondylitis. As peptide presentation by HLA molecules is of central importance for immune responses, we performed thermodynamic (circular dichroism, differential scanning calorimetry, fluorescence polarization) and X-ray crystallographic analyses of both HLA-B27 subtypes complexed with the epidermal growth factor response factor 1-derived self-peptide TIS (RRLPIFSRL) to understand the impact of the Asp116His exchange on peptide display. This peptide is known to be presented in vivo by both subtypes, and as expected for a self-peptide, TIS-reactive cytotoxic T lymphocytes are absent in the respective individuals. The thermodynamic analyses reveal that both HLA-B27:TIS complexes exhibit comparable, relatively high thermostability (Tm approximately 60 degrees C) and undergo multi-step unfolding reactions, with dissociation of the peptide in the first step. As shown by X-ray crystallography, only subtle structural differences between the subtypes were observed regarding the architecture of their F pockets, including the presence of distinct networks of water molecules. However, no consistent structural differences were found between the peptide presentation modes. In contrast to other peptides displayed by the two HLA-subtypes which show either structural or dynamical differences in their peptide presentation modes, the TIS-complexed HLA-B*2705 and HLA-B*2709 subtypes are an example for thermodynamic and structural equivalence, in agreement with functional data.

Binding Sites↗

PubMed2005

Clinical and radiographic subtypes of vascular cognitive impairment in a clinic-based cohort study.

BACKGROUND AND PURPOSE: There is a need for empirical studies to define criteria for vascular cognitive impairment (VCI) subtypes. In this paper, we report the predictive validity of a subtype classification scheme based on clinical and radiographic features. METHODS: Nine Canadian memory clinics participated in the Consortium to Investigate Vascular Impairment of Cognition. This cohort consisted of 1347 patients, of whom 324 had VCI, and was followed for up to 30 months. RESULTS: Clinical and neuroimaging features defined three subtypes: vascular cognitive impairment, no dementia, (n=97), vascular dementia (n=101) and mixed neurodegenerative/vascular dementia (n=126). Any ischemic lesion on neuroimaging increased the odds (odds ratio=9.31; 95% confidence interval 6.46, 13.39) of a VCI diagnosis. No VCI subtype, however, was associated with a specific neuroimaging abnormality. Compared to those with no cognitive impairment, patients with each VCI subtype had higher rates of death and institutionalization (hazard ratio for combined adverse events=6.08, p<0.001). CONCLUSIONS: Both clinical features and radiographic features help establish a diagnosis of VCI. The outcomes of VCI subtypes, however, are more strongly associated with clinical features than with radiographic ones.

Aged↗

PubMed2026

Clinical outcomes and genomic features of uncommon EGFR exon 19 deletion subtypes in osimertinib-treated non-small cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) exon 19 deletion subtypes may be associated with differential survival outcomes following EGFR-tyrosine kinase inhibitor treatment. However, evidence remains scarce, particularly regarding osimertinib, and the underlying biological mechanisms are poorly understood. We aimed to compare survival outcomes among EGFR exon 19 deletion subtypes in patients with non-small cell lung cancer (NSCLC) treated with osimertinib. METHODS: In this multicenter retrospective study, patients with NSCLC were stratified according to exon 19 deletion subtypes. Whole-exome sequencing data from the American Association for Cancer Research Genomics Evidence Neoplasia Information Exchange registry and Memorial Sloan Kettering Clinicogenomic Harmonized Oncologic Real-World Dataset were analyzed to investigate co-occurring genomic alterations. RESULTS: Overall, 111 patients with advanced EGFR exon 19 deletion-positive NSCLC were analyzed and 86.5% received osimertinib as first-line therapy. Patients with non-E746_A750del (n = 25) had shorter progression-free survival (PFS) than those with E746_A750del (n = 86) (median: 14.3 vs. 20.6 months; p < 0.05). Among non-E746_A750del subtypes, L747_A750delinsP (n = 4) had a particularly poor prognosis, with significantly worse survival than those with E746_A750del (median PFS: 3.5 vs. 20.6 months; p < 0.001, and median overall survival: 11.8 vs. 48.5 months; p < 0.001). In public database analyses, non-E746_A750del had a higher rate of RBM10 co-mutations, whereas L747_A750delinsP was characterized by frequent CDKN2A/B homozygous deletions and MYC amplifications. CONCLUSIONS: Non-E746_A750del was associated with poorer outcomes, with L747_A750delinsP potentially being a high-risk subtype. Differences in co-occurring genomic alterations may contribute to the prognostic heterogeneity among exon 19 deletion subtypes.

Humans↗

PubMed2004

Genetic analysis of Indian HIV-1 nef: subtyping, variability and implications.

HIV-1 subtype C is predominant in India and globally. In the present study, we analyze HIV-1 subtype C regulatory protein Nef sequences from five recent Indian seroconverters and five long-term survivors (LTSs) for variability at crucial functional domains. Sequence analysis suggested the possibility of using regulatory gene sequences for viral subtyping and evolutionary studies apart from structural genes. In the phylogenetic tree, Indian nef sequences segregated away from other reported subtype C sequences, forming an Indian subclade within subtype C. Our studies also suggested no evidence for the association of truncated Nef with slow progression of disease, as all LTSs had intact Nef. We could identify some variations in juxtapositions to crucial functional domains, especially in seroconverter sequences, when comparing them with others. In phylogenetic analysis, specifically for the base-pair regions 411-428 and 478-525, our seroconverter sequences segregated away from those reported earlier in the literature, indicating specific evolutionary changes in these conserved regions of nef in currently circulating viruses. But the dN/dS ratio for our samples was less than one on comparing them with reported subtype C and representative sequences of different clades, strongly emphasizing the necessity of sequence conservation at different disease stages and even across clades. HLA-I binding epitope predictions for common Indian HLAs indicated that specific mutations in seroconverter Nef may alter the intensity of epitope binding, which may alter the outcome of the immune response. Hence these data would be useful in designing Nef epitopes to be included in multi-epitope HIV-1 vaccine for the Indian population and would also be of immense help in HIV-1 evolutionary studies.

Adult↗

PubMed2006

Mycoplasma pneumoniae subtype-independent induction of proinflammatory cytokines in THP-1 cells.

Mycoplasma pneumoniae can be divided into two main subtypes depending on the amino acid sequences of the P1 adhesin and the P65 protein, both located in the attachment organelle. Differences between these subtypes in infectivity, virulence and interaction with host cells have not been extensively studied. Using ELISA to measure released protein and real-time PCR to quantify mRNA, we have demonstrated that both M. pneumoniae subtypes significantly increased tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) at comparable levels in THP-1 cells over a 72 h period of time. However, subtype 2 induced a statistically significant increase (P<0.001) in the release of interleukin-1beta at 24 h post-infection compared to subtype 1. These data provide evidence that the induction of proinflammatory cytokine gene and protein expression by M. pneumoniae is not dependent on the infecting subtype.

Cell Line↗

PubMed2004

Changes of 5-HT receptor subtype mRNAs in rat dorsal root ganglion by bee venom-induced inflammatory pain.

The reverse transcriptase polymerase chain reaction (RT-PCR) technique was used to examine the changes of the expression of 5-hydroxytryptamine (5-HT) receptors in the rat lumbar dorsal root ganglion (DRG) following subcutaneous bee venom (BV) injection into the plantar surface of the unilateral hindpaw. In the DRG ipsilateral to the BV injection, significant increase of mRNA levels of 5-HT(1A), 5-HT(1B), 5-HT(2A) and 5-HT(3) receptor subtypes were observed at 1 and 4h after the BV injection, while increase of 5-HT(2C), 5-HT(4), 5-HT(6) and 5-HT(7) receptor subtype mRNAs was detected at 4h only. No such changes were observed in the expressions of 5-HT(1D), 5-HT(1F) and 5-HT(5A) receptor subtype mRNAs. Upregulation of 5-HT(1A), 5-HT(1B) and 5-HT(2A) receptor subtype mRNAs was also observed in the contralateral DRG at 4 h. The presence of 5-HT(1E), 5-HT(2B) and 5-HT(5B) receptor subtype mRNAs was not detected in the rat DRG. The present results suggest that different sets of 5-HT receptor subtypes work at different stages of the inflammatory pain induced by subcutaneous BV injection.

Animals↗

PubMed2006

The role of NMDAR subtypes and charge transfer during hippocampal LTP induction.

Activation of NMDA receptors (NMDARs) is a requirement for persistent synaptic alterations, such as long-term potentiation of synaptic transmission (LTP). NMDARs are composed of NR1 and NR2 subunits, and NR2 subunit-dependent gating properties of NMDAR subtypes cause dramatic differences in the timing of charge transfer. These postsynaptic temporal profiles are further influenced by the frequency of synaptic activation. Here, we investigated in the CA1 region of hippocampal slices from P28 mice, whether particular NMDAR subtypes are recruited based on NR2 subunit-specific gating following different induction protocols. For high frequency afferent stimulation (HFS), we found that genetic impairment of NR2A or pharmacological block of NR2A- or NR2B-type NMDARs can reduce field LTP. In contrast, when pairing low frequency synaptic stimulation with postsynaptic depolarization (LFS pairing) in single CA1 neurons, pharmacological antagonism of either subtype modestly reduced the charge transfer during LFS pairing without reducing the LTP magnitude. These results indicate that HFS-triggered LTP is induced by more than one NMDAR subtype, whereas a single subtype is sufficient during LFS pairing. Analysis of charge transfer during LFS pairing in 13 different conditions revealed a threshold for LTP induction, which was independent of the NR2 antagonist tested. Thus, at least for LFS pairing, the amount of charge transfer, and thus Ca2+ influx, during LTP induction is a factor more critical than the participation of a particular NMDAR subtype.

Animals↗

PubMed2006

Induction of local and systemic immune reactions following infection of turkeys with avian Metapneumovirus (aMPV) subtypes A and B.

Most of the studies regarding the immunopathogenesis of avian Metapneumovirus (aMPV) have been done with subtype C of aMPV. Not much is known about the immunopathogenesis of aMPV subtypes A and B in turkeys. Specifically, local immune reactions have not been investigated yet. We conducted two experiments in commercial turkeys. We investigated local and systemic humoral and cell mediated immune reactions following infection with an attenuated vaccine strain of aMPV subtype B (Experiment I) and virulent strains of aMPV subtypes A and B (Experiment II). Turkeys infected with virulent aMPV strains developed mild respiratory signs while birds inoculated with the attenuated aMPV did not show any clinical signs. Virus neutralizing antibodies were detected locally in tracheal washes and systemically in serum as soon as 5-7 days post aMPV infection (PI) independent of the strain used. Virus neutralizing antibody titres peaked at 7 days PI and then antibody levels declined. The peak of serum ELISA antibody production varied between infected groups and ranged from 14 and 28 days PI. All aMPV strains induced an increase in the percentage of CD4+ T cell populations in spleen and Harderian gland at days 7 or 14 PI. Furthermore, as shown in Experiment I, infection with the attenuated aMPV-B strain stimulated spleen leukocytes to release significantly higher levels of interferons (IFNs), interleukin-6 and nitric oxide in ex vivo culture in comparison to virus-free controls up to 7 days PI (P<0.05). As detected by quantitative real time RT-PCR in Experiment II, infection with virulent aMPV induced an increased IFNgamma expression in the Harderian gland in comparison to virus-free controls. IFNgamma expression in the spleen varied between aMPV strains and days PI. Overall, our study demonstrates that aMPV subtypes A and B infection induced humoral and cell mediated immune reactions comparable to subtype C infections. We observed only temporary stimulation of serum virus neutralizing antibodies and of most of the local immune reactions independent of the aMPV strain used. The temporary character of immune reactions may explain the short duration of protection against challenge following aMPV vaccination in the field.

Animals↗

PubMed2005

Analysis of HIV-1 subtype B third variable region peptide motifs for induction of neutralizing antibodies against HIV-1 primary isolates.

The HIV-1 gp120 V3 loop is a potent inducer of neutralizing antibodies for T cell line adapted-HIV-1, but less so for primary isolates. We hypothesized that peptides representative of the diversity of natural HIV-1 V3 loop variants might capture elements of conserved higher order structures and so stimulate broadly reactive neutralizing antibodies. We designed a panel of 29 subtype B V3 sequences postulated to reflect the range of V3 diversity. These peptides were used to immunize guinea pigs. The most effective peptide (62.19) clustered around the subtype B consensus sequence and induced antibodies that reproducibly neutralized 31% of the subtype B HIV-1 primary isolates evaluated, but exhibited limited cross-neutralization of non-subtype B HIV-1 strains. Taken together, these data demonstrated that the limited neutralization profile of antibodies induced by optimal subtype B V3 motifs likely represents the maximum breadth of neutralization of subtype B HIV-1 primary isolates attainable by anti-V3 peptide antibodies.

Amino Acid Motifs↗

PubMed2005

Construction and characterization of an infectious molecular clone of HIV-1 subtype A of Indian origin.

India has the second highest number of HIV-1 infected people next to South Africa. The predominant proportion of HIV-1 circulating in India is of subtype C origin, with a small fraction made up of subtypes A and B. In this report, we describe the construction and characterization of the first full-length infectious molecular clone p1579A-1 HIV-1, from an HIV-1 subtype A infected person from India, using long PCR and successive ligation of the amplimers. Phylogenetic analysis of the sequence of the entire proviral DNA and LTR confirmed p1579A-1 to be an HIV-1 subtype A. Analysis of the env gene of p1579A-1 showed a conserved GPGQ motif and the absence of basic amino acids at positions 11 and 25 suggesting CCR5 coreceptor usage. Analysis of env N-linked glycosylation sites revealed fewer sites in the V1 region of envelope compared to other subtype A. Transcription factor binding site analysis of the LTR sequences identified conserved as well as unique transcription factor binding sites (TFBS) in p1579A-1. This infectious clone of HIV-1 can be useful to study the molecular mechanism of dominance of subtype C in India.

Adolescent↗