21 research outputs found

    Phylogeographic Analysis of HIV-1 Subtype C Dissemination in Southern Brazil

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    The HIV-1 subtype C has spread efficiently in the southern states of Brazil (Rio Grande do Sul, Santa Catarina and Paraná). Phylogeographic studies indicate that the subtype C epidemic in southern Brazil was initiated by the introduction of a single founder virus population at some time point between 1960 and 1980, but little is known about the spatial dynamics of viral spread. A total of 135 Brazilian HIV-1 subtype C pol sequences collected from 1992 to 2009 at the three southern state capitals (Porto Alegre, Florianópolis and Curitiba) were analyzed. Maximum-likelihood and Bayesian methods were used to explore the degree of phylogenetic mixing of subtype C sequences from different cities and to reconstruct the geographical pattern of viral spread in this country region. Phylogeographic analyses supported the monophyletic origin of the HIV-1 subtype C clade circulating in southern Brazil and placed the root of that clade in Curitiba (Paraná state). This analysis further suggested that Florianópolis (Santa Catarina state) is an important staging post in the subtype C dissemination displaying high viral migration rates from and to the other cities, while viral flux between Curitiba and Porto Alegre (Rio Grande do Sul state) is very low. We found a positive correlation (r2 = 0.64) between routine travel and viral migration rates among localities. Despite the intense viral movement, phylogenetic intermixing of subtype C sequences from different Brazilian cities is lower than expected by chance. Notably, a high proportion (67%) of subtype C sequences from Porto Alegre branched within a single local monophyletic sub-cluster. These results suggest that the HIV-1 subtype C epidemic in southern Brazil has been shaped by both frequent viral migration among states and in situ dissemination of local clades

    HIV infection and antiretroviral therapy lead to unfolded protein response activation

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    Made available in DSpace on 2015-08-19T13:49:24Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) pedro_ferreira_etal_IOC_2015.pdf: 1599099 bytes, checksum: 22a61fd30368b25e600124db68072fd0 (MD5) Previous issue date: 2015Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunologia Aplicada. Florianópolis, SC, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil.Centro de Hematologia e Hemoterapia de Santa Catarina. Florianópolis, SC, Brasil.Hospital Regional Homero de Miranda Gomes. São José, SC, Brasil.Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Imunologia. São Paulo, Sp, BrasilBackground: The unfolded protein response (UPR) is one of the pathways triggered to ensure quality control of the proteins assembled in the endoplasmic reticulum (ER) when cell homeostasis is compromised. This mechanism is primarily composed of three transmembrane proteins serving as stress sensors: PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1). These three proteins’ synergic action elicits translation and transcriptional downstream pathways, leading to less protein production and activating genes that encode important proteins in folding processes, including chaperones. Previous reports showed that viruses have evolved mechanisms to curtail or customize this UPR signaling for their own benefit. However, HIV infection’s effect on the UPR has scarcely been investigated. Methods: This work investigated UPR modulation by HIV infection by assessing UPR-related protein expression under in vitro and in vivo conditions via Western blotting. Antiretroviral (ARV) drugs’ influence on this stress response was also considered. Results: In in vitro and in vivo analyses, our results confirm that HIV infection activates stress-response components and that ARV therapy contributes to changes in the UPR’s activation profile. Conclusions: This is the first report showing UPR-related protein expression in HIV target cells derived directly from HIV-infected patients receiving different ARV therapies. Thus, two mechanisms may occur simultaneously: interference by HIV itself and the ARV drugs’ pharmacological effects as UPR activators. New evidence of how HIV modulates the UPR to enhance its own replication and secure infection success is also presented

    Molecular epidemiology of HIV-1 in Santa Catarina State confirms increases of subtype C in Southern Brazil.

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    Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-11T16:22:38Z No. of bitstreams: 1 Locateli D. Molecular....pdf: 182648 bytes, checksum: 93e90c3cf5e279ef1db4c007c1ef8cbb (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-11T16:22:47Z (GMT) No. of bitstreams: 1 Locateli D. Molecular....pdf: 182648 bytes, checksum: 93e90c3cf5e279ef1db4c007c1ef8cbb (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-02-11T16:35:14Z (GMT) No. of bitstreams: 1 Locateli D. Molecular....pdf: 182648 bytes, checksum: 93e90c3cf5e279ef1db4c007c1ef8cbb (MD5)Made available in DSpace on 2015-02-11T16:35:14Z (GMT). No. of bitstreams: 1 Locateli D. Molecular....pdf: 182648 bytes, checksum: 93e90c3cf5e279ef1db4c007c1ef8cbb (MD5) Previous issue date: 2007UFSC. Laboratório de Imunologia Aplicada. Departamento de Microbiologia e Parasitologia. Florianópolis, SC, BrasilUFSC. Laboratórios de Protozoologia e de Bioinformática. Departamento de Microbiologia e Parasitologia. Florianópolis, SC, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. FBDC. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. FBDC. Salvador, BA, BrasilHospital Regional Homero de Miranda Gomes. São José, SC, BrasilUFSC. Laboratório de Imunologia Aplicada. Departamento de Microbiologia e Parasitologia. Florianópolis, SC, BrasilInstituto Adolfo Lutz. Laboratório de Retrovírus. São Paulo, SP, BrasilUFSC. Laboratórios de Protozoologia e de Bioinformática. Departamento de Microbiologia e Parasitologia. Florianópolis, SC, BrasilUFSC. Laboratório de Imunologia Aplicada. Departamento de Microbiologia e Parasitologia. Florianópolis, SC, BrasilRecent studies have demonstrated an increased prevalence of human immunodeficiency virus type 1 (HIV-1) subtype C in southern Brazil. Although Santa Catarina State (SC) is located in this area and presents one of the country's highest incidences of HIV/AIDS, knowledge on the molecular epidemiology of HIV-1 in such State is lacking. The aim of this study was to investigate the HIV-1 molecular diversity and epidemiological profile of HIV-1-infected patients from SC. DNA samples were PCR amplified and HIV-1 subtypes were determined using both env and gag genes by direct sequencing. Phylogenetic analyses revealed that 48% were subtype C and 23% were subtype B. Possible recombinant forms were observed for both B/C (23%) and B/F (6%) subtypes. Our results, for the first time, identifies HIV-1 subtype C as a major clade circulating in SC and contributes to the understanding of HIV epidemics in the country by confirming the epidemic spread of the HIV-1 subtype C in southern Brazil

    Bayesian MCC tree for HIV-1 subtype C <i>pol</i> (PR/RT) sequences circulating in Brazil.

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    <p>Branches are colored according to the most probable location state of their descendent nodes. The legend for the colors is shown on the left. Brackets indicate the monophyletic clade formed by subtype C sequences sampled from Brazil, and the position of subtype C reference sequences of African origin used to root the tree. The box highlights the position of the sub-cluster BR-PA. The state posterior probability is indicated only at key nodes. Horizontal branch lengths are drawn to scale with the bar at the bottom indicating years.</p

    Bayesian MCMC test of phylogenetic isolation of Brazilian HIV-1 subtype C sequences by geographic region.

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    a<p>Expected AI or PS value under the null hypothesis of no phylogenetic clustering of isolates by sampling location. PA: Porto Alegre. FL: Florianópolis. CU: Curitiba.</p

    ML phylogenetic tree for HIV-1 subtype C <i>pol</i> (PR/RT) sequences circulating in Brazil.

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    <p>The color of a branch represents the geographic region from where the subtype C strain was sampled, according to the legend given in the figure. Brackets indicate the monophyletic clade formed by Brazilian subtype C sequences and the position of subtype C reference sequences of African origin. The box highlights the position of the sub-cluster circulating in Porto Alegre (BR-PA). The <i>aLRT</i> support values are indicated only at key nodes. Horizontal branch lengths are drawn to scale with the bar at the bottom indicating nucleotide substitutions per site. The tree was rooted using HIV-1 subtype A1 and F1 reference sequences.</p
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