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Resistin is an adipocytokine with a proposed dual role in metabolism and inflammation. In light of the ability to promote inflammatory responses, adipocytokines may prove key factors in modulating the host response to HIV. This st...
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Resistin is an adipocytokine with a proposed dual role in metabolism and inflammation. In light of the ability to promote inflammatory responses, adipocytokines may prove key factors in modulating the host response to HIV. This study utilizes the simian immunodeficiency virus (SIV) model of HIV/AIDS to investigate changes in serum resistin levels following dietary intervention and SIV infection and determine associations with measures of body composition and disease severity. Resistin levels, body composition (n = 34), and insulin resistance (n = 16) were determined in healthy rhesus macaques. A subset of animals (n = 8) was placed on an atherogenic diet (AD) and subsequently inoculated with SIVmac239. Longitudinal measures of serum resistin, cytokines, viral load, lymphocyte subsets, and body composition were obtained. In healthy macaques consuming a standard diet, resistin levels correlated positively with total fat mass (r = 0.49; p < 0.01) and tissue fat percent (r = 0.53; p < 0.01) but failed to associate with measures of insulin resistance. In contrast, a negative correlation was noted between these measures of adiposity and resistin following SIV inoculation (r = −0.27; p < 0.05 and r = −0.24; p < 0.05, respectively). Viral load correlated positively with serum resistin (r = 0.32; p < 0.01). Serum levels of MCP-1 and sTNF RII demonstrated no correlation with resistin in normal animals on a standard diet, while a significant positive correlation was observed following SIV infection (r = 0.52; p < 0.0001 and r = 0.59; p < 0.0001, respectively). Findings indicate a fundamental difference in the relationship between resistin and body composition following SIV infection and suggest that elevations in resistin parallel measures of disease severity including loss of body fat and viral replication.
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Swine influenza virus (SIV) is one of the most important zoonotic agents and the origin of the most recent pandemic virus. Asia is considered to be the epicenter for genetic exchanging of influenza A viruses and Southeast Asia inc...
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Swine influenza virus (SIV) is one of the most important zoonotic agents and the origin of the most recent pandemic virus. Asia is considered to be the epicenter for genetic exchanging of influenza A viruses and Southeast Asia including Thailand serves as a reservoir to maintain the persistence of the viruses for seeding other regions. Therefore, searching for new reassortants in this area has been routinely required. Although SIVs in Thailand have been characterized, collective information regarding their genetic evolution and gene constellations is limited. In this study, whole genomes of 30 SIVs isolated during clinical target surveillance plus all available sequences of past and currently circulating Thai SIVs were genetically characterized based on their evolutionary relationships. All genetic pools of Thai SIVs are comprised of four lineages including classical swine (CS), Eurasian swine (EAs), Triple reassortants (TRIG) and Seasonal human (Shs). Out of 84 isolates, nine H1N1, six H3N2 and one H1N2 strains were identified. Gene constellations of SIVs in Thailand are highly complex resulting from multiple reassortments among concurrently circulating SIVs and temporally introduced foreign genes. Most strains contain gene segments from both EAs and CS lineages and appeared transiently. TRIG lineage has been recently introduced into Thai SIV gene pools. The existence of EAs and TRIG lineages in this region may increase rates of genetic exchange and diversity while Southeast Asia is a persistent reservoir for influenza A viruses. Continual monitoring of SIV evolution in this region is crucial in searching for the next potential pandemic viruses.
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Live attenuated simian immunodeficiency virus (SIV) vaccine protects rhesus macaques from high-dose vaginal challenge by pathogenic SIV strain mac251 by maintaining epithelial integrity in the female genital tract to prevent virus...
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Live attenuated simian immunodeficiency virus (SIV) vaccine protects rhesus macaques from high-dose vaginal challenge by pathogenic SIV strain mac251 by maintaining epithelial integrity in the female genital tract to prevent virus entry at the mucosa.
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Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Opiates are well known to modulate immune responses by preventing the development of cell-mediated ...
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Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Opiates are well known to modulate immune responses by preventing the development of cell-mediated immune responses. Their effect on the pathogenesis of HIV-1 infection however remains controversial. Using the simian immunodeficiency virus/macaque model of HIV pathogenesis, we sought to explore the impact of morphine on disease progression and pathogenesis. Sixteen rhesus macaques were divided into two groups; four were administered saline and 12 others morphine routinely. Both groups of animals were then inoculated with SIVmacR71/17E and followed longitudinally for disease pathogenesis. The morphine group (M+V) exhibited a trend towards higher mortality rates and retardation in weight gain compared to the virus-alone group. Interestingly, a subset of M+V animals succumbed to disease within weeks post-infection. These rapid progressors also exhibited a higher incidence of other end-organ pathologies. Despite the higher numbers of circulating CD4+ and CD8+ T cells in the M+V group, CD4/CD8 ratios between the groups remained unchanged. Plasma and CSF viral load in the M+V group was at least a log higher than the control group. Similarly, there was a trend toward increased virus build-up in the brains of M+V animals compared with controls. A novel finding of this study was the increased influx of infected monocyte/macrophages in the brains of M+V animals.
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An important focus in vaccine research is the design of vaccine vectors with low seroprevalence and high immunogenicity. Replication-incompetent lymphocytic choriomeningitis virus (rLCMV) vectors do not elicit vector-neutralizing ...
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An important focus in vaccine research is the design of vaccine vectors with low seroprevalence and high immunogenicity. Replication-incompetent lymphocytic choriomeningitis virus (rLCMV) vectors do not elicit vector-neutralizing antibody responses, and homologous prime-boost regimens with rLCMV vectors induce boostable and protective T cell responses to model antigens in mice. However, cellular and humoral immune responses following homologous rLCMV vaccine regimens have not been rigorously evaluated in non-human primates (NHPs). To test whether rLCMV vectors constitute an effective vaccine platform in NHPs, we developed rLCMV vectors expressing SIVmac239 Env and Gag antigens and assessed their immunogenicity in mice and cynomolgus macaques. Immunization with rLCMV vaccine vectors expressing SIV Env and Gag was effective at generating Sly-specific T cell and antibody responses in both mice and NHPs. Epitope mapping using SIN/ Env in C57BL/6 mice demonstrated that rLCMV vectors induced sustained poly-functional responses to both dominant and subdominant epitopes. Our results suggest the potential of rLCMV vectors as vaccine candidates. Future SIV challenge experiments in rhesus macaques will be needed to assess immune protection by these vaccine vectors. (C) 2016 The Authors. Published by Elsevier Ltd.
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W czerwcu 2006 r. minelo 25 lat od pierwszego opisu przypadków zachorowań na AIDS (acquired immunodeficiency syndome - zespól nabytego uposledzenia odpornosci) (4). AIDS stal sie pandemia, która spowodowala do 2005 r. 39,5 mil...
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W czerwcu 2006 r. minelo 25 lat od pierwszego opisu przypadków zachorowań na AIDS (acquired immunodeficiency syndome - zespól nabytego uposledzenia odpornosci) (4). AIDS stal sie pandemia, która spowodowala do 2005 r. 39,5 miliona zakazeń doroslych i dzieci (o 2,6 miliona wiecej niz w 2004 r.) i przyczynila sie do 2,9 milionów zgonów (37). Epicentrum epidemii stanowia kraje Afryki lezace na poludnie od Sahary: 2A doroslych i dzieci zakazonych HIV zyje na tym obszarze, 3A zgonów spowodowanychAIDS na swiecie dotyczy mieszkańców Afryki subsaharyskiej.
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The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious pro...
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The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of SIVmac239 (a pathogenic, wild-type strain), SIVΔ3 (the live attenuated vaccine strain derived from SIVmac239), or SIVΔ3+ (a pathogenic progeny virus that had evolved from SIVΔ3). All six monkeys developed immunodeficiency and progressed to fatal disease. Although many divergent mutations arose in env among the different hosts, three regions consistently mutated in all monkeys studied; these similar mutations developed independently even though the animals had received only a single infectious molecular clone rather than standard viral inocula that contain viral quasispecies. Together, these data indicate that the env genes of SIVmac239, SIVΔ3, and SIVΔ3+, in the context of different proviral backbones, evolve similarly in different hosts during disease progression.
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Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Delta 9-tetrahydrocannabinol (Delta 9-THC) did not inc...
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Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Delta 9-tetrahydrocannabinol (Delta 9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Delta 9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Delta 9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Delta 9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Delta 9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Delta 9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.
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Many studies have documented how extensively HIV-1 and related viruses interact with host cells. Virus-host interactions are of two conceptual types. First, viruses have evolved to make use of numerous host-cell functions to facil...
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Many studies have documented how extensively HIV-1 and related viruses interact with host cells. Virus-host interactions are of two conceptual types. First, viruses have evolved to make use of numerous host-cell functions to facilitate their own replication. Second, hosts have evolved a number of activities to inhibit virus replication. Understanding the scope and details of HIV-host interactions has been an extraordinary rich scientific endeavor, and in addition to their biomedical importance, studies in this area have established HIV as a model system in virology. Here, I present an overview of how HIV-1 interacts with some key host cell factors during its replication cycle.
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