Identification of the epitopes targeted by antibodies that can neutralize diverse HIV-1 strains can provide important clues for the design of a preventative vaccine.
We have developed a computational approach that can identify key amino acids within the HIV-1 envelope glycoprotein that influence sensitivity to broadly cross-neutralizing antibodies. Given a sequence alignment and neutralization titers for a panel of viruses, the method works by fitting a phylogenetic model that allows the amino acid frequencies at each site to depend on neutralization sensitivities. Sites at which viral evolution influences neutralization sensitivity were identified using Bayes factors (BFs) to compare the fit of this model to that of a null model in which sequences evolved independently of antibody sensitivity. Conformational epitopes were identified with a Metropolis algorithm that searched for a cluster of sites with large Bayes factors on the tertiary structure of the viral envelope.
The recent outbreak of H7N9 influenza virus infections in humans in China has raised concerns about the pandemic potential of this strain. Here we test the efficacy of H3-stalk based chimeric hemagglutinin universal influenza virus vaccine constructs to protect against H7N9 challenge in mice. Chimeric hemagglutinin constructs protected from viral challenge in the context of different administration routes, and a generic oil-in-water adjuvant similar to formulations licensed for use in humans.
Virology at Coursera Watching the Watchers.org One of my goals as a science communicator is to be Earth's virology professor. To do this I teach an undergraduate virology course at Columbia University and at iTunes University.
St.Jude Children’s Research Hospital scientists report that avian H2N2 influenza A viruses related to 1957-1958 pandemic infect human cells and spread among ferrets; may aid identification of emerging threats...
Viruses are no fun to get. It may come as a surprise then that a new form of cancer treatment actually infects patients with viruses to help them. How does this treatment work? Which specific age group is it aimed at to help?
Papillomaviruses have a remarkable infection cycle that depends on the development of a stratified epithelium. The virus infects the lower, dividing layers of the epithelium and viral genomes replicate at low copy number, and are maintained in these cells, for long periods of time. As infected cells differentiate and move to the surface of the epithelium, they switch on high level viral DNA replication, synthesize capsid proteins and form new viral particles. Viral replication takes place in nuclear foci and is dependent on the E1 and E2 replication proteins. Brd4 is a cellular chromatin binding protein that interacts with E2 and is important for transcriptional regulation of papillomaviruses. In this study we examine the role of Brd4 at different stages in the formation of viral replication foci. In the absence of viral DNA replication, Brd4 links the viral proteins to host chromatin. However, when viral genomes begin to amplify to high levels, Brd4 is displaced from nuclear foci and is not required for replication.
Scientists have found cases of Middle East Respiratory Syndrome (MERS) in camels in Qatar, health officials said on Thursday, fuelling speculation that camels might be the animal reservoir that allowed the virus to infect and kill humans.
The company 23andMe will no longer provide health information to people who purchase its DNA testing kit, it announced last night.The change was "to comply with the U.S. Food and Drug Administration’s directive to discontinue new consumer access during our regulatory review process," the statement said. While current customers will still have access to a 23andMe online database noting the health issues associated with their particular DNA, the company will not update that information, and customers who purchased its Personal Genome Service (PGS) on or after 22 November will receive only information about their ancestry and their raw genetic data without interpretation.
The latest version of PEAKS Studio has been released by Bioinformatics Solutions, Inc. PEAKS Studio 7 is a complete software package for proteomics mass spectrometry data analysis and the updates provide improved accuracy.
Scientists at The Scripps Research Institute have determined the most detailed picture yet of a crucial part of the hepatitis C virus, which the virus uses to infect liver cells. The new data reveal unexpected structural features of this protein.
By tracing ancient human DNA, scientists are learning that prehistoric humans may have immigrated and diversified earlier and more frequently -- and there were a lot more of them -- than we previously realized. An analysis of the oldest known human genetic material found that a new collection of 400,000-year-old hominins -- ancient humans -- may be a common ancestor to Neanderthals and Denisovans. The findings were published in the journal Nature this week and they give us new clues about the origins of modern humans.
Hopes of a total cure for HIV have been dealt a blow, after researchers in the US discovered that the "reservoir" of inactive viruses in a patient's body may be up to 60 times larger than previously thought.
Although modern drug treatments have proved hugely effective at controlling the HIV virus, enabling patients to live long and full lives and reducing infection rates, they do not kill all the viruses in an infected individual.
These viruses remain a threat because they can become active again if a patient stops taking their antiretroviral drugs. The findings, published in the journal Cell following a study at the Howard Hughes Medical Institute (HHMI) in Maryland, were "discouraging" experts said, but should re-focus efforts to make sure HIV positive people are getting the treatment they need.
"The findings suggest that there are a lot more of these proviruses that we have to worry about than we thought," said Robert Siliciano, an HHMI investigator at The Johns Hopkins University, who led the new study. "It doesn't mean that it's hopeless, but it does mean we need to focus on getting an even clearer idea of the scope of the problem."
In HIV positive patients the virus targets the immune system's T cells, and becomes integrated into the cell's genes, making the cell reproduce the virus. Antiretroviral drugs target these active forms of the virus, but in some cells, the virus remains inactive. It is this type of virus that researchers now believe is far more numerous than previously thought. As of yet, researchers have no way of eradicating inactive HIV viruses.
E. coli showing evolution? Yes! Researchers at Michigan State University have been growing Escherichia coli for 25 years, which is over 58,000 generations, in a project called the Long-Term Experimental Evolution project. And during this time, through studying 12 populations of E. coli, they have found that the bacteria continues to adapt to its environment, with no upper limit in sight- even in the 40,00-50,000 generation range, E. coli‘s “fitness” (a measure of how the organism has adapted to its environment) increased by 3-4% per generation!
Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.
Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009.