Elucidation of Hepatitis C Virus Transmission and Early Diversification by Single Genome Sequencing

A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures

No neon, but jets in the remarkable recurrent nova M31N 2008-12a? - Hubble Space Telescope spectroscopy of the 2015 eruption

The 2008 discovery of an eruption of M31N 2008-12a began a journey on which the true nature of this remarkable recurrent nova continues to be revealed. M31N 2008-12a contains a white dwarf close to the Chandrasekhar limit, accreting at a high rate from its companion, and undergoes thermonuclear eruptions which are observed yearly and may even be twice as frequent. In this paper, we report on Hubble Space Telescope STIS UV spectroscopy taken within days of the predicted 2015 eruption, coupled with Keck spectroscopy of the 2013 eruption. Together, this spectroscopy permits the reddening to be constrained to E(B-V) = 0.10 +/- 0.03. The UV spectroscopy reveals evidence for highly ionized, structured, and high velocity ejecta at early times. No evidence for neon is seen in these spectra however, but it may be that little insight can be gained regarding the composition of the white dwarf (CO vs ONe)

No neon, but jets in the remarkable recurrent nova M31N 2008-12a? - Hubble Space Telescope spectroscopy of the 2015 eruption

The 2008 discovery of an eruption of M31N 2008-12a began a journey on which the true nature of this remarkable recurrent nova continues to be revealed. M31N 2008-12a contains a white dwarf close to the Chandrasekhar limit, accreting at a high rate from its companion, and undergoes thermonuclear eruptions which are observed yearly and may even be twice as frequent. In this paper, we report on Hubble Space Telescope STIS UV spectroscopy taken within days of the predicted 2015 eruption, coupled with Keck spectroscopy of the 2013 eruption. Together, this spectroscopy permits the reddening to be constrained to E(B-V) = 0.10 +/- 0.03. The UV spectroscopy reveals evidence for highly ionized, structured, and high velocity ejecta at early times. No evidence for neon is seen in these spectra however, but it may be that little insight can be gained regarding the composition of the white dwarf (CO vs ONe)

Estimating time since infection in early homogeneous HIV-1 samples using a poisson model

<p>Abstract</p> <p>Background</p> <p>The occurrence of a genetic bottleneck in HIV sexual or mother-to-infant transmission has been well documented. This results in a majority of new infections being homogeneous, <it>i.e</it>., initiated by a single genetic strain. Early after infection, prior to the onset of the host immune response, the viral population grows exponentially. In this simple setting, an approach for estimating evolutionary and demographic parameters based on comparison of diversity measures is a feasible alternative to the existing Bayesian methods (<it>e.g</it>., BEAST), which are instead based on the simulation of genealogies.</p> <p>Results</p> <p>We have devised a web tool that analyzes genetic diversity in acutely infected HIV-1 patients by comparing it to a model of neutral growth. More specifically, we consider a homogeneous infection (<it>i.e</it>., initiated by a unique genetic strain) prior to the onset of host-induced selection, where we can assume a random accumulation of mutations. Previously, we have shown that such a model successfully describes about 80% of sexual HIV-1 transmissions provided the samples are drawn early enough in the infection. Violation of the model is an indicator of either heterogeneous infections or the initiation of selection.</p> <p>Conclusions</p> <p>When the underlying assumptions of our model (homogeneous infection prior to selection and fast exponential growth) are met, we are under a very particular scenario for which we can use a forward approach (instead of backwards in time as provided by coalescent methods). This allows for more computationally efficient methods to derive the time since the most recent common ancestor. Furthermore, the tool performs statistical tests on the Hamming distance frequency distribution, and outputs summary statistics (mean of the best fitting Poisson distribution, goodness of fit p-value, etc). The tool runs within minutes and can readily accommodate the tens of thousands of sequences generated through new ultradeep pyrosequencing technologies. The tool is available on the LANL website.</p

Humoral Response to the Anopheles gambiae Salivary Protein gSG6: A Serological Indicator of Exposure to Afrotropical Malaria Vectors

Salivary proteins injected by blood feeding arthropods into their hosts evoke a saliva-specific humoral response which can be useful to evaluate exposure to bites of disease vectors. However, saliva of hematophagous arthropods is a complex cocktail of bioactive factors and its use in immunoassays can be misleading because of potential cross-reactivity to other antigens. Toward the development of a serological marker of exposure to Afrotropical malaria vectors we expressed the Anopheles gambiae gSG6, a small anopheline-specific salivary protein, and we measured the anti-gSG6 IgG response in individuals from a malaria hyperendemic area of Burkina Faso, West Africa. The gSG6 protein was immunogenic and anti-gSG6 IgG levels and/or prevalence increased in exposed individuals during the malaria transmission/rainy season. Moreover, this response dropped during the intervening low transmission/dry season, suggesting it is sensitive enough to detect variation in vector density. Members of the Fulani ethnic group showed higher anti-gSG6 IgG response as compared to Mossi, a result consistent with the stronger immune reactivity reported in this group. Remarkably, anti-gSG6 IgG levels among responders were high in children and gradually declined with age. This unusual pattern, opposite to the one observed with Plasmodium antigens, is compatible with a progressive desensitization to mosquito saliva and may be linked to the continued exposure to bites of anopheline mosquitoes. Overall, the humoral anti-gSG6 IgG response appears a reliable serological indicator of exposure to bites of the main African malaria vectors (An. gambiae, Anopheles arabiensis and, possibly, Anopheles funestus) and it may be exploited for malaria epidemiological studies, development of risk maps and evaluation of anti-vector measures. In addition, the gSG6 protein may represent a powerful model system to get a deeper understanding of molecular and cellular mechanisms underlying the immune tolerance and progressive desensitization to insect salivary allergens

Nursing in the hospital accreditation process: practice and implications in the work quotidian

The aim of this study was to investigate the role and influence of nursing in the hospital accreditation process. It is a qualitative study, conducted in a private hospital of Belo Horizonte. The study subjects were nine nurses and 15 nursing technicians. Data collection was through semi-structured interviews, which were subjected to content analysis. The results showed that the role of the nursing team in the accreditation involves care, administrative, educational and research issues. The study subjects presented different perceptions regarding the influence of the accreditation process in their work. The positive aspects of personal growth and valorization of the curriculum were highlighted as well as negative aspects such as stress and little professional valorization. Therefore, it is necessary that the professionals understand the logic of the process and act with a view to the interdisciplinarity and overcoming the fragmentation of care, thus achieving integral healthcare and the quality of care desired.Este estudio investigó el papel y la influencia de la enfermería en el proceso de acreditación de hospitales. Se trata de un estudio cualitativo realizado en un hospital en Belo Horizonte. Los sujetos del estudio fueron 09 enfermeras y 15 técnicos de enfermería. Los datos fueron recolectados a través de entrevistas semiestructuradas, las que fueron sometidas a análisis de contenido. Los resultados mostraron que la actuación de la enfermería en el proceso de acreditación implica cuestiones relacionadas con la atención, administración, educación e investigación. Los profesionales tenían percepciones diferentes acerca de la influencia del proceso de acreditación en su trabajo. Se destacaron aspectos positivos como el crecimiento personal y el desarrollo del currículo; los negativos fueron estrés y poco desarrollo profesional. Por lo anterior es necesario que los profesionales entiendan la lógica del proceso y actúen con una finalidad interdisciplinaria superando la fragmentación en el cuidado, logrando así la atención integral y la calidad de la atención.Os objetivos neste estudo foram conhecer a atuação e as influências da enfermagem no processo de acreditação hospitalar. Trata-se de pesquisa qualitativa, realizada em um hospital privado de Belo Horizonte, MG. Esta pesquisa ficou composta por nove enfermeiros e quinze técnicos de enfermagem. Os dados foram coletados por meio de entrevistas com roteiro semiestruturado, submetidas à análise de conteúdo. Os resultados mostraram que a atuação da enfermagem na acreditação envolve questões assistenciais, administrativas, educativas e de pesquisa. Os sujeitos da pesquisa apresentaram percepções diversas sobre a influência do processo de acreditação no seu trabalho. Foram destacados aspectos positivos como crescimento pessoal e valorização do currículo e aspectos negativos como estresse e pouca valorização profissional. Assim, é necessário que os profissionais entendam a lógica do processo, atuem com vistas à interdisciplinaridade e superação da fragmentação da assistência, alcançando assim o cuidado integral e a qualidade assistencial desejada

Dry weather induces outbreaks of human West Nile virus infections

<p>Abstract</p> <p>Background</p> <p>Since its first occurrence in the New York City area during 1999, West Nile virus (WNV) has spread rapidly across North America and has become a major public health concern in North America. By 2002, WNV was reported in 40 states and the District of Columbia with 4,156 human and 14,539 equine cases of infection. Mississippi had the highest human incidence rate of WNV during the 2002 epidemic in the United States. Epidemics of WNV can impose enormous impacts on local economies. Therefore, it is advantageous to predict human WNV risks for cost-effective controls of the disease and optimal allocations of limited resources. Understanding relationships between precipitation and WNV transmission is crucial for predicting the risk of the human WNV disease outbreaks under predicted global climate change scenarios.</p> <p>Methods</p> <p>We analyzed data on the human WNV incidences in the 82 counties of Mississippi in 2002, using standard morbidity ratio (SMR) and Bayesian hierarchical models, to determine relationships between precipitation and human WNV risks. We also entertained spatial autocorrelations of human WNV risks with conditional autocorrelative (CAR) models, implemented in WinBUGS 1.4.3.</p> <p>Results</p> <p>We observed an inverse relationship between county-level human WNV incidence risk and total annual rainfall during the previous year. Parameters representing spatial heterogeneity in the risk of human exposure to WNV improved model fit. Annual precipitation of the previous year was a predictor of spatial variation of WNV risk.</p> <p>Conclusions</p> <p>Our results have broad implications for risk assessment of WNV and forecasting WNV outbreaks. Assessing risk of vector-born infectious diseases will require understanding of complex ecological relationships. Based on the climatologically characteristic drought occurrence in the past and on climate model predictions for climate change and potentially greater drought occurrence in the future, we suggest that the frequency and relative risk of WNV outbreaks could increase.</p

Stochastic Theory of Early Viral Infection: Continuous versus Burst Production of Virions

Viral production from infected cells can occur continuously or in a burst that generally kills the cell. For HIV infection, both modes of production have been suggested. Standard viral dynamic models formulated as sets of ordinary differential equations can not distinguish between these two modes of viral production, as the predicted dynamics is identical as long as infected cells produce the same total number of virions over their lifespan. Here we show that in stochastic models of viral infection the two modes of viral production yield different early term dynamics. Further, we analytically determine the probability that infections initiated with any number of virions and infected cells reach extinction, the state when both the population of virions and infected cells vanish, and show this too has different solutions for continuous and burst production. We also compute the distributions of times to establish infection as well as the distribution of times to extinction starting from both a single virion as well as from a single infected cell for both modes of virion production

Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues

It has recently been estimated that a single HIV-1 infected cell produces between and more than viral particles over its life span. Since body-wide estimates of the ratio of free virus to productively infected cells are smaller than and much smaller than , individual virions must be cleared rapidly. This seems difficult to reconcile with the fact that most of the total body virus is trapped on follicular dendritic cells where it can survive for many months. It has also been difficult to reconcile the vast difference in the rates at which the virus is cleared from the blood in rhesus macaques and in chronically infected patients. Here we attempt to reconcile these seemingly contradictory observations by considering the virion clearance rate in various organs and the virion exchange rates between them. The main results are that the per capita clearance rate of free virus in lymphoid tissue should be fast, the virion exchange rate between lymphoid tissue and the blood should be slow, and the comparatively slow previous estimates for the virion clearance rate from the blood correspond to the rate of virion efflux from the blood to other organs where the virus is ultimately cleared