RESUMEN
The chemokine SDF-1 (CXCL12) and its receptor CXCR4 control several processes during embryonic development such as the regulation of stem cell proliferation, differentiation, and migration. However, the role of this pathway in the formation of the pituitary gland is not understood. We sought to characterise the expression patterns of CXCR4, SDF-1 and CXCR7 at different stages of pituitary gland development. Our expression profiling revealed that SDF-1 is expressed in progenitor-rich regions of the pituitary anterior lobe, that CXCR4 and CXCR7 have opposite expression domains and that CXCR4 expression is conserved between mice and human embryos. We then assessed the importance of this signalling pathway in the development and function of the murine pituitary gland through conditional deletion of CXCR4 in embryonic pituitary progenitors. Successful and specific ablation of CXCR4 expression in embryonic pituitary progenitors did not lead to observable embryonic nor postnatal defects but allowed the identification of stromal CXCR4+ cells not derived from HESX1+ progenitors. Further analysis of constitutive SDF-1, CXCR7 and CXCR4 mutants of the pathway indicates that CXCR4 expression in HESX1+ cells and their descendants is not essential for normal pituitary development in mice.
Asunto(s)
Receptores CXCR , Animales , Femenino , Humanos , Ratones , Embarazo , Diferenciación Celular , Quimiocina CXCL12/metabolismo , Embrión de Mamíferos/metabolismo , Proteínas de Homeodominio/metabolismo , Receptores CXCR/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Proteínas Represoras/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND/AIM: Glioblastoma (GB) is the most aggressive type of tumor in the central nervous system and is characterized by resistance to therapy and abundant vasculature. Tumor vessels contribute to the growth of GB, and the tumor microenvironment is thought to influence tumor vessels. We evaluated the molecular communication between human GB cells and human brain microvascular endothelial cells (HBMEC) in vitro. MATERIALS AND METHODS: We investigated whether GB-conditioned media (GB-CM) influenced HBMEC proliferation and migration, as well as the levels of MMP-9, CXCL12, CXCR4, CXCR7, VEGFs, VEGFR-2, and WNT5a in HBMEC. RESULTS: Although HBMEC proliferation was not modified, increased HBMEC migration was detected after GB-CM treatment. Furthermore, treatment of HBMEC with GB-CM resulted in increased levels of MMP-9 and CXCR4. The levels of WNT5a, VEGFs and VEGFR-2 were not affected. CONCLUSION: GB-secreted factors lead to increased endothelial cell migration and to increased levels of MMP-9 and CXCR4.
Asunto(s)
Neoplasias Encefálicas/patología , Encéfalo/patología , Movimiento Celular , Células Endoteliales/patología , Glioblastoma/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Receptores CXCR4/metabolismo , Neoplasias Encefálicas/genética , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quimiocina CXCL12/metabolismo , Medios de Cultivo Condicionados/farmacología , Células Endoteliales/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/genética , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores CXCR/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Proteína Wnt-5a/genética , Proteína Wnt-5a/metabolismoRESUMEN
AIM: To examine the interference of ß-blockers with the chemokine stromal cell-derived factor-1 (SDF-1) found in cell homing receptors, C-X-C chemokine receptor type 4 (CXCR-4) and CXCR-7, and regulatory proteins of homing pathways, we administered atenolol, carvedilol, metoprolol, and propranolol for 30 days using an orogastric tube to hypertensive rats. METHOD: We collected blood samples before and after treatment and quantified the levels of SDF-1 with enzyme-linked immunosorbent assay (ELISA). On day 30 of treatment, the spontaneously hypertensive rats (SHR) were euthanized, and heart, liver, lung, and kidney tissues were biopsied. Proteins were isolated for determining the expression of CXCR-4, CXCR-7, GRK-2 (G protein-coupled receptors kinase 2), ß-arrestins (ß1-AR and ß2-AR), and nuclear factor kappa B (NFκB). RESULTS: We found that the study drugs modulated these proteins, and metoprolol and propranolol strongly affected the expression of ß1-AR (P = .0102) and ß2-AR (P = .0034). CONCLUSION: ß-blockers modulated tissue expression of the proteins and their interactions following 30 days of treatment. It evidences that this class of drugs can interfere with proteins of cell homing pathways.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Antihipertensivos/farmacología , Movimiento Celular/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Animales , Atenolol/farmacología , Carbazoles/farmacología , Carvedilol , Quimiocina CXCL12/sangre , Modelos Animales de Enfermedad , Quinasa 2 del Receptor Acoplado a Proteína-G/metabolismo , Hipertensión/sangre , Hipertensión/fisiopatología , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Metoprolol/farmacología , Miocardio/metabolismo , FN-kappa B/metabolismo , Propanolaminas/farmacología , Propranolol/farmacología , Ratas Endogámicas SHR , Receptores CXCR/metabolismo , Receptores CXCR4/metabolismo , Transducción de Señal/efectos de los fármacos , beta-Arrestina 1/metabolismo , Arrestina beta 2/metabolismoRESUMEN
BACKGROUND: Cell homing is the mechanism by which an injury releases signaling molecules that cause recruitment, proliferation, migration and differentiation of progenitor cells. Stromal derived factor-1 (SDF-1) and its receptor CXCR4 are key molecules involved in homing and little is known about their activation in cardiopathies. Here, we assessed the homing activation status of bone marrow cells (BMC) concerning the SDF-1 and CXCR4 expression in ischemic (IHD) and valvular (VHD) heart diseases. METHODS: The SDF-1 and inflammatory profile were analyzed by ELISA from plasma obtained bone marrow of ischemic heart patients (IHD, n = 41), valvular heart patients (VHD, n = 30) and healthy controls (C, n = 9). Flow cytometry was used to evaluate CXCR4 (CD184) expression on the surface of bone marrow cells, and the CXCR4 expression was estimated by real-time quantitative PCR. RESULTS: The SDF-1 levels in the groups IHD, VHD and control were, respectively, 230, 530 and 620 pg/mL (P = 0.483), and was decreased in VHD patients using beta-blockers (263 pg/mL) when compared with other (844 pg/mL) (P = 0.023). Compared with IHD, the VHD group showed higher CXCR4 (P = 0.071) and CXCR7 (P = 0.082) mRNA expression although no difference in the level of CXCR4+ bone marrow cells was found between groups (P = 0.360). CONCLUSION: In conclusion, pathophysiological differences between IHD and VHD can affect the molecules involved in the activation of homing. In addition, the use of beta-blockers appears to interfere in this mechanism, a fact that should be considered in protocols that use BMC.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Células de la Médula Ósea/citología , Enfermedades de las Válvulas Cardíacas/terapia , Células Madre Mesenquimatosas/citología , Isquemia Miocárdica/terapia , Adulto , Anciano , Biomarcadores/metabolismo , Células de la Médula Ósea/metabolismo , Quimiocina CXCL12/metabolismo , Femenino , Enfermedades de las Válvulas Cardíacas/genética , Enfermedades de las Válvulas Cardíacas/patología , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Isquemia Miocárdica/genética , Isquemia Miocárdica/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores CXCR/genética , Receptores CXCR/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
CXCR4 was the first receptor identified for CXCL12, but a second receptor, CXCR7, has also been described and its function in hematopoietic cells remains unknown. By inhibition of CXCR4 and/or CXCR7, we showed that CXCR7 participates in normal CD34+ and U937 cell migration and prevents downregulation of CXCR4 by CXCL12 stimulation. In addition, CXCR7 contributes to homing of acute myeloid leukemia and normal progenitor cells to the bone marrow and spleen of NOD/SCID mice. In summary, this study shows an essential role of CXCR7, together with CXCR4, in the control of normal and malignant hematopoietic cell migration and homing induced by CXCL12.
Asunto(s)
Movimiento Celular , Quimiocina CXCL12/metabolismo , Células Madre Hematopoyéticas/metabolismo , Leucemia Mieloide Aguda/metabolismo , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/metabolismo , Receptores CXCR/metabolismo , Animales , Células Madre Hematopoyéticas/patología , Xenoinjertos , Humanos , Leucemia Mieloide Aguda/patología , Ratones , Ratones Desnudos , Ratones SCID , Trasplante de Neoplasias , Células Madre Neoplásicas/patología , Células U937RESUMEN
Breast cancer (BrC) is a major public health problem worldwide. The intra-tumoral heterogeneity and tumor cell plasticity importantly contribute to disease progression and treatment failure. However, the dynamic interactions between different tumor clones, as well as their contribution to tumor aggressiveness are still poorly understood. In this study, we provide evidence of a lateral transmission of aggressive features between aggressive and non-aggressive tumor cells, consisting of gain of expression of cancer stem cell markers, increased expression of CXCL12 receptors CXCR4 and CXCR7 and increased invasiveness in response to CXCL12, which correlated with high levels of secretion of pro-inflammatory mediators G-CSF, GM-CSF, MCP-1, IL-8 and metalloproteinases 1 and 2 by the aggressive cells. Noteworthy, we found no evidence of a TGF-ß participation in the inducible-invasive phenotype. Altogether, our results provide evidence of communication between tumor cells with different potentials for aggressiveness, which could influence intra-tumoral population dynamics promoting the emergence of clones with novel functions. Understanding these interactions will provide better targets for diagnosis, prognosis and therapeutic strategies.
Asunto(s)
Neoplasias de la Mama/genética , Evolución Clonal/genética , Heterogeneidad Genética , Invasividad Neoplásica/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Linaje de la Célula/genética , Movimiento Celular , Proliferación Celular/genética , Quimiocina CXCL12/genética , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica/patología , Receptores CXCR/genética , Receptores CXCR4/genética , Transducción de Señal , Factor de Crecimiento Transformador beta/genéticaRESUMEN
With the hypothesis that blocking chemokine signaling can ameliorate acute laminitis, the aim was to evaluate the therapeutic effect of intravenous DF1681B, a selective antagonist for CXCR1 and CXCR2 (chemokine receptors), in an oligofructose equine laminitis model. To twelve mixed breed clinically healthy hoses with no previous history of hoof-related lameness was administered oligofructose (10g/kg given by nasogastric tube) and divided into two groups: treated (intravenous DF1681B at 30mg/kg 6, 12, 18, and 24h after oligofructose) and non-treated groups. Laminar biopsies were performed before and 12, 36, and 72h after administering oligofructose. Samples were stained with periodic acid-Schiff (PAS) and scored from 0 to 6 according to epidermal cell and basal membrane changes. The IL-1β, IL-6, and CXCL1 RNA expressions were determined by RT-PCR. Parametric and non-parametric tests were used to compare times within each group (P<0.05). The PAS grades and IL-1β and IL-6 RNA expression increased in the non-treated group, but remained constant in the treated horses. In conclusion, DF1681B therapy reduced laminar inflammation and epidermal deterioration in treated horses. CXCR1/2 blockage should be considered therapeutically for equine acute laminitis(AU)
A expressão de quimiocinas e a infiltração de leucócitos no tecido laminar são característicos de laminite aguda de equinos. O presente estudo avaliou o efeito terapêutico da administração intravenosa de DF1681B , um antagonista seletivo para CXCR1 e CXCR2 (receptores de quimiocinas), em um modelo de laminite equina por oligofrutose. Utilizaram-se doze cavalos sem raça definida, compreendendo quatro machos e oito fêmeas não gestantes, com idade (média ±SD) 7±3,5 anos, pesando 305±35kg e com uma pontuação média de condição corporal de 5±1/9. Os indivíduos elegíveis eram clinicamente saudáveis, sem história prévia de claudicação relacionados ao casco. Após administração de oligofrutose (10g/kg por sonda nasogástrica), os animais foram divididos em dois grupos: tratado (30mg/kg de DF1681B intravenosa, 6, 12, 18 e 24h após a oligofrutose) e não tratado, que recebeu placebo. Biópsias laminares foram realizadas antes e 12, 36 e 72h após a administração de oligofrutose. As amostras foram coradas com ácido periódico de Schiff (PAS) e classificadas de 0-6 de acordo com alterações nas células epidérmicas e na membrana basal. Também determinaram-se as expressões gênicas de IL-1β, CXCL1 e IL-6 por RT-PCR. Testes paramétricos e não paramétricos foram utilizados para comparar os momentos em cada grupo (P<0,05). Estatisticamente, os graus PAS e as expressões de IL-1β e IL-6 se elevaram após a indução no grupo não tratado, mas se mantiveram constantes nos cavalos tratados. Em conclusão, a terapia por DF1681B reduziu a inflamação laminar e a deterioração epidérmica em equinos submetidos ao modelo de intoxicação por oligofructose. O bloqueio de receptores CXCR1/2 deve ser considerado como uma opção terapêutica para prevenção da laminite aguda de equinos(AU)
Asunto(s)
Animales , Caballos/fisiología , Quimiocinas/antagonistas & inhibidores , Prebióticos , Neutrófilos/patología , Receptores CXCR/antagonistas & inhibidores , Biopsia/veterinaria , Pezuñas y Garras/patología , Técnicas Histológicas/veterinariaRESUMEN
With the hypothesis that blocking chemokine signaling can ameliorate acute laminitis, the aim was to evaluate the therapeutic effect of intravenous DF1681B, a selective antagonist for CXCR1 and CXCR2 (chemokine receptors), in an oligofructose equine laminitis model. To twelve mixed breed clinically healthy hoses with no previous history of hoof-related lameness was administered oligofructose (10g/kg given by nasogastric tube) and divided into two groups: treated (intravenous DF1681B at 30mg/kg 6, 12, 18, and 24h after oligofructose) and non-treated groups. Laminar biopsies were performed before and 12, 36, and 72h after administering oligofructose. Samples were stained with periodic acid-Schiff (PAS) and scored from 0 to 6 according to epidermal cell and basal membrane changes. The IL-1β, IL-6, and CXCL1 RNA expressions were determined by RT-PCR. Parametric and non-parametric tests were used to compare times within each group (P<0.05). The PAS grades and IL-1β and IL-6 RNA expression increased in the non-treated group, but remained constant in the treated horses. In conclusion, DF1681B therapy reduced laminar inflammation and epidermal deterioration in treated horses. CXCR1/2 blockage should be considered therapeutically for equine acute laminitis.
A expressão de quimiocinas e a infiltração de leucócitos no tecido laminar são característicos de laminite aguda de equinos. O presente estudo avaliou o efeito terapêutico da administração intravenosa de DF1681B , um antagonista seletivo para CXCR1 e CXCR2 (receptores de quimiocinas), em um modelo de laminite equina por oligofrutose. Utilizaram-se doze cavalos sem raça definida, compreendendo quatro machos e oito fêmeas não gestantes, com idade (média ±SD) 7±3,5 anos, pesando 305±35kg e com uma pontuação média de condição corporal de 5±1/9. Os indivíduos elegíveis eram clinicamente saudáveis, sem história prévia de claudicação relacionados ao casco. Após administração de oligofrutose (10g/kg por sonda nasogástrica), os animais foram divididos em dois grupos: tratado (30mg/kg de DF1681B intravenosa, 6, 12, 18 e 24h após a oligofrutose) e não tratado, que recebeu placebo. Biópsias laminares foram realizadas antes e 12, 36 e 72h após a administração de oligofrutose. As amostras foram coradas com ácido periódico de Schiff (PAS) e classificadas de 0-6 de acordo com alterações nas células epidérmicas e na membrana basal. Também determinaram-se as expressões gênicas de IL-1β, CXCL1 e IL-6 por RT-PCR. Testes paramétricos e não paramétricos foram utilizados para comparar os momentos em cada grupo (P<0,05). Estatisticamente, os graus PAS e as expressões de IL-1β e IL-6 se elevaram após a indução no grupo não tratado, mas se mantiveram constantes nos cavalos tratados. Em conclusão, a terapia por DF1681B reduziu a inflamação laminar e a deterioração epidérmica em equinos submetidos ao modelo de intoxicação por oligofructose. O bloqueio de receptores CXCR1/2 deve ser considerado como uma opção terapêutica para prevenção da laminite aguda de equinos.
Asunto(s)
Animales , Caballos/fisiología , Neutrófilos/patología , Prebióticos , Quimiocinas/antagonistas & inhibidores , Receptores CXCR/antagonistas & inhibidores , Biopsia/veterinaria , Pezuñas y Garras/patología , Técnicas Histológicas/veterinariaRESUMEN
Novel therapies need to be developed for patients with pancreatic cancer because of the poor outcomes of current regimens. Pancreatic cancer cells respond to the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C chemokine receptor type 7 (CXCR7)/C-X-C motif chemokine 12 (CXCL12)/high-mobility group box 1 signaling axis and this axis presents a novel target for therapy. C-X-C motif chemokine 12 stimulates CXCR4/CXCR7-bearing cells in a paracrine manner. C-X-C chemokine receptor type 4 and CXCR7 are transmembrane G protein-coupled receptors that, upon interaction with ligand CXCL12, activate downstream protein kinases that promote a more aggressive behavior. C-X-C chemokine receptor type 4 is expressed on most pancreatic cancer cells, whereas CXCR7 is primarily expressed on tumor-associated endothelium. High-mobility group box 1 promotes the CXCR4 and CXCL12 interaction, promoting angiogenesis and lymphangiogenesis. Hypoxia-inducible factor 1 is a potent stimulator of CXCR4 and CXCL12 expression, promoting more aggressive behavior. This receptor/ligand interaction can be disrupted by CXCR4 antagonists available and in clinical use to harvest bone marrow stem cells. Novel imaging strategies are now being developed at several centers to evaluate response to therapy and identify early recurrence. Thus, the CXCR4/CXCR7/CXCL12 interaction plays a critical role in cancer cell progression, proliferation, invasion, as well as metastasis and is a suitable target for therapy, imaging, as well as development of novel diagnostics.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Quimiocina CXCL12/metabolismo , Proteína HMGB1/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Antineoplásicos/uso terapéutico , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Receptores CXCR4/antagonistas & inhibidoresRESUMEN
Recently, a novel CXCL12-binding receptor, has been identified. This CXCL12-binding receptor commonly known as CXCR7 (CXC chemokine receptor 7), has lately, based on a novel nomenclature, has received the name ACKR3 (atypical chemokine receptor 3). In this study, we aimed to investigate the expression of CXCR7 in leukemic cells, as well as its participation in CXCL12 response. Interesting, we clearly demonstrated that CXCR7 is highly expressed in acute lymphoid leukemic cells compared with myeloid or normal hematopoietic cells and that CXCR7 contributed to T-acute lymphoid leukemic cell migration induced by CXCL12. Moreover, we showed that the cellular location of CXCR7 varied among T-lymphoid cells and this finding may be related to their migration capacity. Finally, we hypothesized that CXCR7 potentiates CXCR4 response and may contribute to the maintenance of leukemia by initiating cell recruitment to bone marrow niches that were once occupied by normal hematopoietic stem cells.
Asunto(s)
Quimiocina CXCL12/farmacología , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Bencilaminas , Western Blotting , Médula Ósea/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Ciclamas , Femenino , Citometría de Flujo , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Compuestos Heterocíclicos/farmacología , Humanos , Células Jurkat , Células K562 , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Interferencia de ARN , Receptores CXCR/sangre , Receptores CXCR/genética , Receptores CXCR4/antagonistas & inhibidores , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células U937 , Adulto JovenRESUMEN
BACKGROUND: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell hyper-reactivity and the production of pathogenic anti-nuclear-directed auto-antibodies (Abs). B-cell ontogeny is partly dependent on the CXCL12/CXCR4 axis for which the contribution to SLE pathogenesis remains unclear. CXCR7, the novel receptor for CXCL12, is differentially expressed among memory B-cell subsets. However, its biological role in SLE remains to be explored. METHODS: Relative CXCR4 and CXCR7 expression levels were compared by quantitative PCR in leukocytes from blood samples of 41 Mexican Mestizos patients with SLE and 45 ethnicity-matched healthy subjects. Intracellular and membrane expression of both receptors was analyzed by flow cytometry in naive and Ab-secreting B cells. B-cell responsiveness to CXCL12 was investigated using Transwell-based chemotaxis assays. Data were analyzed using the Kruskal-Wallis test for comparisons of values amongst healthy controls and patients with inactive or active SLE, and non-parametrically using the Mann-Whitney U-test for multiple comparisons and unpaired samples. Correlations were determined by Spearman's ranking. RESULT: SLE leukocytes displayed reduced levels of CXCR4 and CXCR7 transcripts. In SLE patients, a significant defect in CXCR4 expression was detected at the surface of naive and Ab-secreting B cells, associated with an abnormal intracellular localization of the receptor. CXCR7 predominantly localized in cytosolic compartments of B cells from healthy and SLE individuals. Disease activity did not impact on these expression patterns. Altered receptor compartmentalization correlated with an impaired CXCL12-promoted migration of SLE B cells. CONCLUSIONS: Our data highlight a down-regulation of CXCL12 receptors on circulating B cells from SLE patients that likely influences their migratory behavior and distribution.
Asunto(s)
Linfocitos B/metabolismo , Etnicidad , Lupus Eritematoso Sistémico/metabolismo , Lupus Eritematoso Sistémico/patología , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Adulto , Linfocitos B/efectos de los fármacos , Linfocitos B/patología , Recuento de Células , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Quimiocina CXCL12/farmacología , Quimiotaxis/efectos de los fármacos , Demografía , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/genética , Masculino , México , Persona de Mediana Edad , Células Plasmáticas/efectos de los fármacos , Células Plasmáticas/metabolismo , Células Plasmáticas/patología , Receptores CXCR/genética , Receptores CXCR4/genética , Adulto JovenRESUMEN
The aim of this study was to investigate HIV-1 molecular diversity and the epidemiological profile of HIV-1-infected patients from Ribeirão Preto, Brazil. A nested PCR followed by sequencing of a 302-base pair fragment of the env gene (C2-V3 region) was performed in samples from HIV-1-positive patients. A total of 45 sequences were aligned with final manual adjustments. The phylogenetic analyses showed a higher prevalence of HIV-1 subtype B in the studied population (97.8%) with only one sample yielding an F1 subtype. The viral genotyping prediction showed that CCR5 tropism was the most prevalent in the studied cohort. Geno2pheno analysis showed that R5 and CXCR4 prediction were 69% and 31%, respectively. There was no statistical significance, either in viral load or in CD4(+) T cell count when R5 and X4 prediction groups were compared. Moreover, the GPGR tetramer was the most common V3 loop core motif identified in the HIV-1 strains studied (34.1%) followed by GWGR, identified in 18.1% of the samples. The high level of B subtype in this Brazilian population reinforces the nature of the HIV epidemic in Brazil, and corroborates previous data obtained in the Brazilian HIV-infected population.