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Genomic Variation in Seven Khoe-San Groups Reveals Adaptation and Complex African History

"The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ∼2.3 million SNPs in 220 southern Africans and found that the Khoe-San diverged from other populations ≥100,000 years ago, but structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa; instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response, potential adaptive introgression of UV-light protection, and selection predating modern human diversification involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history."

 

Ex Africa, semper aliquid novi...or old, in this case!

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Virology and Bioinformatics from Virology.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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It's a group effort - the curators:

It's a group effort - the curators: | Virology and Bioinformatics from Virology.ca | Scoop.it

get in touch if you want to help curate this topic

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Human H7N9 and H5N1 influenza viruses differ in induction of cytokines and tissue tropism

Since emerging in 2013, the avian-origin H7N9 influenza viruses have resulted in over 400 human infections leading to 115 deaths to date. Although the epidemiology differs from human highly pathogenic avian H5N1 influenza infections, there is a similar rapid progression to acute respiratory distress syndrome (ARDS). The aim of these studies was to compare the pathological and immunological characteristics of a panel of human H7N9 and H5N1 viruses in vitro and in vivo. Although there were similarities between particular H5N1 and H7N9 viruses, including association between lethal disease and spread to the alveolar spaces and kidney, there were also strain-specific differences. Both H5N1 and H7N9 viruses are capable of causing lethal infections, with mortality correlating most strongly with wider distribution of viral antigen in the lungs, rather than with traditional measures of viral titer and host responses. Strain-specific differences included hypercytokinemia in H5N1 infections that was not seen with the H7N9 infections regardless of lethality. Conversely, H7N9 viruses showed a greater tropism for respiratory epithelium covering nasal passages and NALT than H5N1 viruses, which may explain the enhanced transmission in ferret models. Overall these studies highlight some distinctive properties of H5N1 and H7N9 viruses in different in vitro and in vivo models.

Importance The novel avian-origin H7N9 pandemic represents a serious threat to public health. The ability of H7N9 to cause serious lung pathology leading in some cases to the development of acute respiratory distress syndrome is of particular concern. Initial reports of H7N9 infection compared them to infections caused by highly pathogenic avian (HPAI) H5N1 viruses. Thus, it is of critical importance to understand the pathology and immunological response to infection with H7N9 as compared to HPAI H5N1 viruses. We compared these responses in both in vitro and in vivo models, and found that H5N1 and H7N9 infections exhibit distinct pathological, immunological and tissue tropism differences that could explain differences in clinical disease and viral transmission.

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Occurrence and reassortment of avian influenza A (H7N9) viruses derived from coinfected birds in China

Over the course of two waves of infection, H7N9 avian influenza A virus has caused 436 human infections and claimed 170 lives in China as of July 2014. To investigate the prevalence and genetic diversity of H7N9 we surveyed avian influenza viruses in poultry in Jiangsu province within the outbreak epicenter. We found frequent occurrence of H7N9/H9N2 co-infection in chickens. Molecular clock phylogenetic analysis confirms co-infection by H7N9/H9N2 viruses and also reveals that the identity of the H7N9 outbreak lineage is confounded by ongoing reassortment between outbreak viruses and diverse H9N2 viruses in domestic birds. Experimental inoculation of a co-infected sample in cell culture yielded two reassortant H7N9 strains with polymerase segments from the original H9N2 strain. Ongoing reassortment between the H7N9 outbreak lineage and diverse H9N2 viruses may generate new strains with the potential to infect humans, highlighting the need for continued viral surveillance in poultry and humans.

Importance We found frequent occurrence of H7N9/H9N2 co-infection in chickens. The H7N9 outbreak lineage is confounded by ongoing reassortment between H7N9 and H9N2 viruses. The importance of H9N2 viruses as the source of novel avian influenza virus infections in humans requires continuous attention.

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How to bury your academic writing

How to bury your academic writing | Virology and Bioinformatics from Virology.ca | Scoop.it
Book chapters can allow freedom to think about your work in line with broader theoretical issues, but if you're tempted to write a book chapter for an edited collection, it might be best to reconsi...
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Ebola - WakaWaka

Ebola - WakaWaka | Virology and Bioinformatics from Virology.ca | Scoop.it
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Ten Simple Rules for Better Figures

Ten Simple Rules for Better Figures | Virology and Bioinformatics from Virology.ca | Scoop.it
PLOS Computational Biology is an open-access
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Filoviruses Require Endosomal Cysteine Proteases for Entry but Exhibit Distinct Protease Preferences

Ken Yaw Agyeman-Badu's insight:

Filoviruses are enveloped viruses that cause sporadic outbreaks of severe hemorrhagic fever [CDC, MMWR Morb. Mortal. Wkly. Rep. 50:73–77, 2001; Colebunders and Borchert, J. Infect. 40:16–20, 2000; Colebunders et al., J. Infect. Dis. 196(Suppl. 2):S148–S153, 2007; Geisbert and Jahrling, Nat. Med. 10:S110-S121, 2004]. Previous studies revealed that endosomal cysteine proteases are host factors for ebolavirus Zaire (Chandran et al., Science 308:1643–1645, 2005; Schornberg et al., J. Virol. 80:4174–4178, 2006). In this report, we show that infection mediated by glycoproteins from other phylogenetically diverse filoviruses are also dependent on these proteases and provide additional evidence indicating that they cleave GP1 and expose the binding domain for the critical host factor Niemann-Pick C1. Using selective inhibitors and knockout-derived cell lines, we show that the ebolaviruses Zaire and Cote d'Ivoire are strongly dependent on cathepsin B, while the ebolaviruses Sudan and Reston and Marburg virus are not. Taking advantage of previous studies of cathepsin B inhibitor-resistant viruses (Wong et al., J. Virol. 84:163–175, 2010), we found that virus-specific differences in the requirement for cathepsin B are correlated with sequence polymorphisms at residues 47 in GP1 and 584 in GP2. We applied these findings to the analysis of additional ebolavirus isolates and correctly predicted that the newly identified ebolavirus species Bundibugyo, containing D47 and I584, is cathepsin B dependent and that ebolavirus Zaire-1995, the single known isolate of ebolavirus Zaire that lacks D47, is not. We also obtained evidence for virus-specific differences in the role of cathepsin L, including cooperation with cathepsin B. These studies strongly suggest that the use of endosomal cysteine proteases as host factors for entry is a general property of members of the family Filoviridae.

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Ken Yaw Agyeman-Badu's curator insight, September 14, 11:22 PM

Filoviruses are enveloped viruses that cause sporadic outbreaks of severe hemorrhagic fever [CDC, MMWR Morb. Mortal. Wkly. Rep. 50:73–77, 2001; Colebunders and Borchert, J. Infect. 40:16–20, 2000; Colebunders et al., J. Infect. Dis. 196(Suppl. 2):S148–S153, 2007; Geisbert and Jahrling, Nat. Med. 10:S110-S121, 2004]. Previous studies revealed that endosomal cysteine proteases are host factors for ebolavirus Zaire (Chandran et al., Science 308:1643–1645, 2005; Schornberg et al., J. Virol. 80:4174–4178, 2006). In this report, we show that infection mediated by glycoproteins from other phylogenetically diverse filoviruses are also dependent on these proteases and provide additional evidence indicating that they cleave GP1 and expose the binding domain for the critical host factor Niemann-Pick C1. Using selective inhibitors and knockout-derived cell lines, we show that the ebolaviruses Zaire and Cote d'Ivoire are strongly dependent on cathepsin B, while the ebolaviruses Sudan and Reston and Marburg virus are not. Taking advantage of previous studies of cathepsin B inhibitor-resistant viruses (Wong et al., J. Virol. 84:163–175, 2010), we found that virus-specific differences in the requirement for cathepsin B are correlated with sequence polymorphisms at residues 47 in GP1 and 584 in GP2. We applied these findings to the analysis of additional ebolavirus isolates and correctly predicted that the newly identified ebolavirus species Bundibugyo, containing D47 and I584, is cathepsin B dependent and that ebolavirus Zaire-1995, the single known isolate of ebolavirus Zaire that lacks D47, is not. We also obtained evidence for virus-specific differences in the role of cathepsin L, including cooperation with cathepsin B. These studies strongly suggest that the use of endosomal cysteine proteases as host factors for entry is a general property of members of the family Filoviridae.

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PolyCTLDesigner: a computational tool for constructing polyepitope T-cell antigens - BMC Research Notes

Construction of artificial polyepitope antigens is one of the most promising strategies for developing more efficient and safer vaccines evoking T-cell immune responses. Epitope rearrangements and utilization of certain spacer sequences have been proven to greatly influence the immunogenicity of polyepitope constructs. However, despite numerous efforts towards constructing and evaluating artificial polyepitope immunogens as well as despite numerous computational methods elaborated to date for predicting T-cell epitopes, peptides binding to TAP and for antigen processing prediction, only a few computational tools were currently developed for rational design of polyepitope antigens.

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Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge : Nature Medicine : Nature Publishing Group

A chimpanzee adenovirus-based vaccination approach elicits acute and long-term protection against ebolavirus challenge in nonhuman primates.

Via Mel Melendrez-Vallard
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Emerging Viral Diseases: Confronting Threats with New Technologies

Abstract

Emerging viral diseases pose ongoing health threats, particularly in an era of globalization; however, new biomedical research technologies such as genome sequencing and structure-based vaccine and drug design have improved our ability to respond to viral threats.

 
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Rabies Rapid Transit System

Rabies Rapid Transit System | Virology and Bioinformatics from Virology.ca | Scoop.it
Rabies virus hijacks the transport systems of neurons, manipulating axonal transport machinery to get to the central nervous system at maximum speed.
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Reverse genetics system could ease norovirus research

Reverse genetics system could ease norovirus research | Virology and Bioinformatics from Virology.ca | Scoop.it
Finding may allow scientists to manipulate viral genome.
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Major alteration in coxsackievirus B3 genomic RNA structure distinguishes a virulent strain from an avirulent strain

Coxsackievirus B3 (CV-B3) is a cardiovirulent enterovirus that utilizes a 5′ untranslated region (5′UTR) to complete critical viral processes. Here, we directly compared the structure of a 5′UTR from a virulent strain with that of a naturally occurring avirulent strain. Using chemical probing analysis, we identified a structural difference between the two 5′UTRs in the highly substituted stem-loop II region (SLII). For the remainder of the 5′UTR, we observed conserved structure. Comparative sequence analysis of 170 closely related enteroviruses revealed that the SLII region lacks conservation. To investigate independent folding and function, two chimeric CV-B3 strains were created by exchanging nucleotides 104–184 and repeating the 5′UTR structural analysis. Neither the parent SLII nor the remaining domains of the background 5′UTR were structurally altered by the exchange, supporting an independent mechanism of folding and function. We show that the attenuated 5′UTR lacks structure in the SLII cardiovirulence determinant.

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U.S. Military to Send 3,000 to Battle Ebola Virus

U.S. Military to Send 3,000 to Battle Ebola Virus | Virology and Bioinformatics from Virology.ca | Scoop.it
The U.S. military will deploy about 3,000 personnel to West Africa to coordinate international aid, build treatment centers and train health-care workers as part of President Barack Obama's offensive against a worsening Ebola outbreak, a senior...

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TLR5-Mediated Sensing of Gut Microbiota Is Necessary for Antibody Responses to Seasonal Influenza Vaccination: Immunity

Systems biological analysis of immunity to the trivalent inactivated influenza vaccine (TIV) in humans revealed a correlation between early expression of TLR5 and the magnitude of the antibody response. Vaccination of Trl5−/− mice resulted in reduced antibody titers and lower frequencies of plasma cells, demonstrating a role for TLR5 in immunity to TIV. This was due to a failure to sense host microbiota. Thus, antibody responses in germ-free or antibiotic-treated mice were impaired, but restored by oral reconstitution with a flagellated, but not aflagellated, strain of E. coli. TLR5-mediated sensing of flagellin promoted plasma cell differentiation directly and by stimulating lymph node macrophages to produce plasma cell growth factors. Finally, TLR5-mediated sensing of the microbiota also impacted antibody responses to the inactivated polio vaccine, but not to adjuvanted vaccines or the live-attenuated yellow fever vaccine. These results reveal an unappreciated role for gut microbiota in promoting immunity to vaccination.

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Basics of the Unix Philosophy

Chris Upton + helpers's insight:

The ‘Unix philosophy’ originated with Ken Thompson's early meditations on how to design a small but capable operating system with a clean service interface. It grew as the Unix culture learned things about how to get maximum leverage out of Thompson's design. It absorbed lessons from many sources along the way.

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Genetically Modified Mosquitoes Pave the Way for Dengue Fever Prevention | Viruses101 | Learn Science at Scitable

Genetically Modified Mosquitoes Pave the Way for Dengue Fever Prevention | Viruses101 | Learn Science at Scitable | Virology and Bioinformatics from Virology.ca | Scoop.it
Over 40% of the word's population is at risk of contracting Dengue Fever, a mosquito borne virus. Scientists are now using genetically modified mosquitoes to try and prevent the spread of Dengue Fever.
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▶ Jonathan Yewdell - How to Succeed in Science - YouTube

Jonathan Yewdell M.D., Ph.D. (NIH) -- leading immunologist and head of NIAID Cell Biology and Viral Immunology -- delivers a grantsmanship lecture on "How to...
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Marburgvirus Resurgence in Kitaka Mine Bat Population after Extermination Attempts

Marburgvirus Resurgence in Kitaka Mine Bat Population after Extermination Attempts | Virology and Bioinformatics from Virology.ca | Scoop.it

Marburg virus (MARV) and Ravn virus (RAVV), collectively called marburgviruses, cause Marburg hemorrhagic fever (MHF) in humans. In July 2007, 4 cases of MHF (1 fatal) occurred in miners at Kitaka Mine in southern Uganda. Later, MHF occurred in 2 tourists who visited Python Cave, ≈50 km from Kitaka Mine. One of the tourists was from the United States (December 2007) and 1 was from the Netherlands (July 2008); 1 case was fatal (1,2,3). The cave and the mine each contained 40,000–100,000 Rousettus aegyptiacus bats (Egyptian fruit bats).

Longitudinal investigations of the outbreaks at both locations were initiated by the Viral Special Pathogens Branch of the Centers for Disease Control and Prevention (CDC, Atlanta, GA, USA, and Entebbe, Uganda) in collaboration with the Uganda Wildlife Authority (UWA) and the Uganda Virus Research Institute (UVRI). During these studies, genetically diverse MARVs and RAVVs were isolated directly from bat tissues, and infection levels of the 2 viruses were found to increase in juvenile bats on a predictable bi-annual basis (4,5). However, investigations at Kitaka Mine were stopped when the miners exterminated the bat colony by restricting egress from the cave with papyrus reed barriers and then entangling the bats in fishing nets draped over the exits. The trapping continued for weeks, and the entrances were then sealed with sticks and plastic. These depopulation efforts were documented by researchers from UVRI, the CDC, the National Institute of Communicable Diseases (Sandringham, South Africa), and UWA during site visits to Kitaka Mine (Technical Appendix[PDF - 124 KB - 1 page] Figure). In August 2008, thousands of dead bats were found piled in the forest, and by November 2008, there was no evidence of bats living in the mine; whether 100% extermination was achieved is unknown. CDC, UVRI, and UWA recommended against extermination, believing that any results would be temporary and that such efforts could exacerbate the problem if bat exclusion methods were not complete and permanent (6,7).

 

Ed Rybicki's insight:

So there's the bats' revenge: exterminate us, and we'll come back with a higher prevalence - with more diverse viruses!

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SearchSmallRNA: a graphical interface tool for the assemblage of viral genomes using small RNA libraries data - Virology Journal

SearchSmallRNA: a graphical interface tool for the assemblage of viral genomes using small RNA libraries data - Virology Journal | Virology and Bioinformatics from Virology.ca | Scoop.it
Next-generation parallel sequencing (NGS) allows the identification of viral pathogens by sequencing the small RNAs of infected hosts. Thus, viral genomes may be assembled from host immune response products without prior virus enrichment, amplification or purification. However, mapping of the vast information obtained presents a bioinformatics challenge.
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Ten Simple Rules for Better Figures

Ten Simple Rules for Better Figures | Virology and Bioinformatics from Virology.ca | Scoop.it

"Scientific visualization is classically defined as the process of graphically displaying scientific data. However, this process is far from direct or automatic. There are so many different ways to represent the same data: scatter plots, linear plots, bar plots, and pie charts, to name just a few. Furthermore, the same data, using the same type of plot, may be perceived very differently depending on who is looking at the figure. A more accurate definition for scientific visualization would be a graphical interface between people and data. In this short article, we do not pretend to explain everything about this interface; rather, see [1], [2] for introductory work. Instead we aim to provide a basic set of rules to improve figure design and to explain some of the common pitfalls."

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ImmunizeCA App - Immunize Canada

ImmunizeCA App - Immunize Canada | Virology and Bioinformatics from Virology.ca | Scoop.it
The Canadian Public Health Association, Immunize Canada and the Ottawa Hospital Research Institute collaborated to develop an app for mobile devices that will help Canadians keep track of their vaccinations. The app is FREE and can be downloaded from iTunes, Google Play of BlackBerry World.
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Microbiology: Bacteria get vaccinated

Microbiology: Bacteria get vaccinated | Virology and Bioinformatics from Virology.ca | Scoop.it
Infection by defective bacterial viruses that cannot replicate has now been found to be the key feature enabling bacteria to rapidly develop adaptive immunity against functional viruses.
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A fish, a rabbit — same thing, to a creationist

A fish, a rabbit — same thing, to a creationist | Virology and Bioinformatics from Virology.ca | Scoop.it
JBS Haldane is said to have responded to a question about how evolution could be disproved by saying, “A Precambrian rabbit”. What was meant by this, of course, is any substantial discovery that greatly disrupted the evidence for the chronological pattern of descent observed in Earth’s life. That pattern of descent is one of the…
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A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection | Virology and Bioinformatics from Virology.ca | Scoop.it

Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-κB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems.

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Human Immunodeficiency Virus gag and protease: partners in resistance

Human Immunodeficiency Virus gag and protease: partners in resistance | Virology and Bioinformatics from Virology.ca | Scoop.it

Human Immunodeficiency Virus (HIV) maturation plays an essential role in the viral life cycle by enabling the generation of mature infectious virus particles through proteolytic processing of the viral Gag and GagPol precursor proteins. An impaired polyprotein processing results in the production of non-infectious virus particles. Consequently, particle maturation is an excellent drug target as exemplified by inhibitors specifically targeting the viral protease (protease inhibitors; PIs) and the experimental class of maturation inhibitors that target the precursor Gag and GagPol polyproteins. Considering the different target sites of the two drug classes, direct cross-resistance may seem unlikely. However, coevolution of protease and its substrate Gag during PI exposure has been observed both in vivo and in vitro. This review addresses in detail all mutations in Gag that are selected under PI pressure. We evaluate how polymorphisms and mutations in Gag affect PI therapy, an aspect of PI resistance that is currently not included in standard genotypic PI resistance testing. In addition, we consider the consequences of Gag mutations for the development and positioning of future maturation inhibitors.

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