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This topic is a collaborative effort:
In 8 May 1980, the World Health Organisation declared that “the world and its peoples are free from smallpox.” Through decades of intense vaccination, this once fatal disease had been wiped out. It was a singular victory and having won it, countries around the world discontinued the vaccination programmes. After all, why protect against a disease that no longer exists, except in a few isolated stocks? Unfortunately, this is not a rhetorical question. The smallpox vaccine did more than protect against smallpox. It also reduced the risk of contracting a related illness called monkeypox, which produces the same combination of scabby bumps and fever. It’s milder than smallpox but it’s still a serious affliction. In Africa, where monkeypox originates from, it kills anywhere from 1-10% of those who are infected. And more and more people are becoming infected. Anne Rimoin from the University of California, Los Angeles compared data on the virus in the Democratic Republic of Congo over the last three decades. She found that, during those years, monkeypox has become 20 times more common in humans. In one particular area, 72 people out of every million were infected each year between 1981 and 1986. Between 2005 and 2007, that figure rose to 1442 per million. Rimoin thinks that we eased up the pressure on smallpox vaccination too soon. Between 1981 and 1985, only 404 cases turned up in all of Africa, and simulations predicted that the disease was unlikely to spread too far in a human population before dying out. This was no public health threat. In 1986, even the monitoring programme was stopped. In 2005 however, Rimoin’s group, together with the DRC Ministry of Health and the World Health Organization set up a new round of monkeypox surveillance and they spent two years collecting data. Their research showed that the disease is gaining ground. Rimoin found that monkeypox was disproportionately affecting children and almost all of those who fell sick were born after 1980, when the smallpox vaccination programme was halted in the DRC. The vaccine wasn’t a perfect defence against monkeypox but it was still around 85% effective. Among people who were born during the vaccination era, those who were immunised were 5 times less likely to develop monkeypox than their protected peers. And this protection is clearly long-lasting; even 25 years on, they could still ward off the related virus. These figures are probably underestimates too. The region’s inconsistent healthcare isn’t exactly conducive to accurate disease monitoring and Rimoin says that her team had word of many more cases, but couldn’t always check them out because of their remote location. Monkeypox is spread by animals including squirrels and, fairly obviously, monkeys. As humans encroach upon the DRC’s tropical rainforests, the risk of being exposed to an infected carrier grows. Indeed, Rimoin found that the odds of contracting monkeypox were higher for people living near forested areas, and for men. As civil strife continues to affect the DRC, locals are being forced to rely more on hunting to get enough food and that brings men in close contact with furry viral reservoirs. It’s an emerging threat, but Rimoin isn’t calling for smallpox vaccination to resume. Doing so would be logistically difficult in an area where even collecting data can be fraught. It might be better to take a more targeted approach, vaccinating only health workers who treat infected patients, and people who come into frequent contact with animal carriers. It may also be worth educating local people about the dangers of handling carrier species and the benefits of isolating people who show the very obvious symptoms, until they can be treated. But most importantly, Rimoin wants active surveillance in regions where the virus circulates, especially since there are still so many unknowns about the virus. We need to better understand how it moves from human to human (and from animal to human), how often it’s fatal, or what the complications are. It’s a good opportunity to take action now, at a time when the monkeypox is still confined to specific areas. Things might not stay that way. In 2003, there was a bizarre outbreak in the United States, as rodents from Ghana brought the disease to American prairie dogs, who handed it over to humans. All sorts of rodents the world over might become reservoirs for the disease and Rimoin writes, “If monkeypox were to become established in a wildlife reservoir outside Africa, the public health setback would be difficult to reverse.”
Via Dr. Stefan Gruenwald
Notably, the evidence presented (a) indicates that proteomes of all species ranging from bacteria to mammals appear to adhere to the same universal constraint (“oil escape”) set into motion by the last common ancestor more than 3.5 billion years ago, (b) indicates the presence of a previously untapped global (composition-level) molecular clock, and (c) strengthens the non-equilibrium/directional view of amino acid substitutions that challenges central dogmas regarding reversibility in molecular evolution.
BACKGROUND: Novel effective anti-influenza agent that tolerates influenza virus antigenic variation is needed. Highly conserved influenza virus M2 protein has multiple pivotal functions including ion channel activity for vRNP uncoating, anti-autophagy and virus assembly, morphogenesis and release. Thus, M2 is an attractive target of anti-influenza agents including small molecular drugs and specific antibodies. METHODS: Fully human monoclonal single chain antibodies (HuScFv) specific to recombinant and native M2 proteins of A/H5N1 virus were produced from huscfv-phagemid transformed E. coli clones selected from a HuScFv phage display library using recombinant M2 of clade 1 A/H5N1 as panning antigen. The HuScFv were tested for their ability to inhibit replication of A/H5N1 of both homologous and heterologous clades. M2 domains bound by HuScFv of individual E. coli clones were identified by phage mimotope searching and computerized molecular docking. RESULTS: HuScFv derived from four huscfv-phagemid transformed E. coli clones (no. 2, 19, 23 and 27) showed different amino acid sequences particularly at the CDRs. Cells infected with A/H5N1 influenza viruses (both adamantane sensitive and resistant) that had been exposed to the HuScFv had reduced virus release and intracellular virus. Phage peptide mimotope search and multiple alignments revealed that conformational epitopes of HuScFv2 located at the residues important for ion channel activity, anti-autophagy and M1 binding; epitopic residues of HuScFv19 located at the M2 amphipathic helix and cytoplasmic tail important for anti-autophagy, virus assembly, morphogenesis and release; epitope of HuScFv23 involved residues important for the M2 activities similar to HuScFv2 and also amphipathic helix residues for viral budding and release while HuScFv27 epitope spanned ectodomain, ion channel and anti-autophagy residues. Results of computerized homology modelling and molecular docking conformed to the epitope identification by phages. CONCLUSIONS: HuScFv that bound to highly conserved epitopes across influenza A subtypes and human pathogenic H5N1clades located on different functional domains of M2 were produced. The HuScFv reduced viral release and intracellular virus of infected cells. While the molecular mechanisms of the HuScFv await experimental validation, the small human antibody fragments have high potential for developing further as a safe, novel and mutation tolerable anti-influenza agent especially against drug resistant variants.
Abstract There is much evidence that some pathogens manipulate the behaviour of their mosquito hosts to enhance pathogen transmission. However, it is unknown whether this phenomenon exists in the interaction of Anopheles gambiae sensu stricto with the malaria parasite, Plasmodium falciparum - one of the most important interactions in the context of humanity, with malaria causing over 200 million human cases and over 770 thousand deaths each year. Here we demonstrate, for the first time, that infection with P. falciparum causes alterations in behavioural responses to host-derived olfactory stimuli in host-seeking female An. gambiae s.s. mosquitoes.
For the first time, scientists have created human embryonic stem cells by transferring the nucleus of a mature cell into an egg. The cloning technique could nudge the dream of personalized medicine closer to reality, researchers suggest May 15 in Cell.
The ability of vaccines to induce T cell responses is crucial for preventing diseases caused by viruses or bacteria. Nanoparticles (NPs) are considered an efficient tool for inducing potent immune responses. In this study, we describe a novel vaccination approach with biodegradable calcium phosphate (CaP) NPs that serve as carrier of immunoactive TLR9 ligand (CpG) combined with a viral Ag from the influenza A virus hemagglutinin. Functionalized CaP NPs were efficiently taken up by dendritic cells in vivo and elicited a potent T cell–mediated immune response in immunized mice with high numbers of IFN-γ–producing CD4+ and CD8+ effector T cells. Most importantly, both i.p. and intranasal immunization with these NPs offered protection in a mouse model of influenza virus infection. This study demonstrates the great potential of CaP NPs as a novel vaccination tool that offers substantial flexibility for several infection models.
During the 2009 H1N1 influenza pandemic, vaccines for the virus became available in large quantities only after human infections peaked. To accelerate vaccine availability for future pandemics, we developed a synthetic approach that very rapidly generated vaccine viruses from sequence data. Beginning with hemagglutinin (HA) and neuraminidase (NA) gene sequences, we combined an enzymatic, cell-free gene assembly technique with enzymatic error correction to allow rapid, accurate gene synthesis. We then used these synthetic HA and NA genes to transfect Madin-Darby canine kidney (MDCK) cells that were qualified for vaccine manufacture with viral RNA expression constructs encoding HA and NA and plasmid DNAs encoding viral backbone genes. Viruses for use in vaccines were rescued from these MDCK cells. We performed this rescue with improved vaccine virus backbones, increasing the yield of the essential vaccine antigen, HA. Generation of synthetic vaccine seeds, together with more efficient vaccine release assays, would accelerate responses to influenza pandemics through a system of instantaneous electronic data exchange followed by real-time, geographically dispersed vaccine production.
Abstract "Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus that causes fatal disease in a wide range of species, including humans. HeV was first described in Australia in 1994, and has continued to re-emerge with increasing frequency. HeV is of significant concern to human health due to its high mortality rate, increasing emergence, absence of vaccines and limited post exposure therapies..."
The origin of life must have required a series of transitions building new levels of molecular interaction. However, a tension often exists between the fitness of an individual sequence and the fitness of the collective. This tension would be important for the earliest replicase enzymes (i.e., replicases), which would help other individuals replicate without helping themselves directly. The proposed solution to this problem is to essentially create small groups of interactors, either by compartmentation or a lattice-like structure. Selection among individuals in the group favors parasites, but selection at the level of the group favors groups with more replicases, thus allowing ‘altruistic’ replicases to survive.
The non-structural protein 1 (NS1) of influenza A virus (IAV), coded by its third most diverse gene, interacts with multiple molecules within infected cells. NS1 is involved in host immune response regulation and is a potential contributor to the virus host range. Early phylogenetic analyses using 50 sequences led to the classification of NS1 gene variants into groups (alleles) A and B. We reanalyzed NS1 diversity using 14,716 complete NS IAV sequences, downloaded from public databases, without host bias. Removal of sequence redundancy and further structured clustering at 96.8% amino acid similarity produced 415 clusters that enhanced our capability to detect distinct subgroups and lineages, which were assigned a numerical nomenclature. Maximum likelihood phylogenetic reconstruction using RNA sequences indicated the previously identified deep branching separating group A from group B, with five distinct subgroups within A as well as two and five lineages within the A4 and A5 subgroups, respectively. Our classification model proposes that sequence patterns in thirteen amino acid positions are sufficient to fit >99.9% of all currently available NS1 sequences into the A subgroups/lineages or the B group. This classification reduces host and virus bias through the prioritization of NS1 RNA phylogenetics over host or virus phenetics. We found significant sequence conservation within the subgroups and lineages with characteristic patterns of functional motifs, such as the differential binding of CPSF30 and crk/crkL or the availability of a C-terminal PDZ-binding motif. To understand selection pressures and evolution acting on NS1, it is necessary to organize the available data. This updated classification may help to clarify and organize the study of NS1 interactions and pathogenic differences and allow the drawing of further functional inferences on sequences in each group, subgroup and lineage rather than on a strain-by-strain basis.
PubMed comprises more than 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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From molecules to physiology
Abstract Interspecies transmission of influenza A is an important factor in the evolution and ecology of influenza viruses. Marine mammals are in contact with a number of influenza reservoirs, including aquatic birds and humans, and this may facilitate transmission among avian and mammalian hosts. Virus isolation, whole genome sequencing, and hemagluttination inhibition assay confirmed that exposure to pandemic H1N1 influenza virus occurred among free-ranging Northern Elephant Seals (Mirounga angustirostris) in 2010. Nasal swabs were collected from 42 adult female seals in April 2010, just after the animals had returned to the central California coast from their short post-breeding migration in the northeast Pacific.
Microbial image of the month
This is a great image of a biofilm growing on a micro-fibrous material. Biofilms are aggregates of bacteria that are coated with a ‘slimy’ substance consisting of polysaccharide, DNA and proteins.
A group of coronavirus experts has published its proposal to name a new, deadly virus after the Middle East, the region where it originates. In a short paper published online today by the Journal of Virology, the Coronavirus Study Group (CSG), along with several other scientists, recommends calling the pathogen Middle East Respiratory Syndrome Coronavirus (MERS-Cov).
Heterogenous nuclear ribonucleoproteins (hnRNPs) control many processes of the gene expression machinery including mRNA transcription, splicing, export, stability and translation.
Influenza virus disease still remains one of the major threats to human health, involving a wide range of animal species and pigs play an important role in influenza ecology. Pigs were labeled as “mixing vessels” since they are susceptible to infection with avian, human and swine influenza viruses and genetic reassortment between these viruses can occur. After the H1N1 influenza pandemic of 2009 with a swine origin virus, the most recent research in “influenzology” is directed at improving knowledge of porcine influenza virus infection. This tendency is probably due to the fact that domestic pigs are closely related to humans and represent an excellent animal model to study various microbial infectious diseases. In spite of the role of the pig in influenza virus ecology, swine immune responses against influenza viruses are not fully understood. Considering these premises, the aim of this review is to focus on the in vitro studies performed with porcine cells and influenza virus and on the immune responses of pigs against human, avian and swine influenza viruses in vivo. The increased acceptance of pigs as suitable and valuable models in the scientific community may stimulate the development of new tools to assess porcine immune responses, paving the way for their consideration as the future “gold standard” large-animal model in immunology.
Abstract "Viruses are usually thought to form parasitic associations with hosts, but all members of the family Polydnaviridae are obligate mutualists of insects called parasitoid wasps. Phylogenetic data founded on sequence comparisons of viral genes indicate that polydnaviruses in the genus Bracovirus (BV) are closely related to pathogenic nudiviruses and baculoviruses. However, pronounced differences in the biology of BVs and baculoviruses together with high divergence of many shared genes make it unclear whether BV homologs still retain baculovirus-like functions..."
Novel effective anti-influenza agent that tolerates influenza virus antigenic variation is needed.
Scientists rarely reuse expert knowledge of phylogeny, in spite of years of effort to assemble a great
Comprehensive Antibiotic Research Database (CARD,arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture and the environment.
PubMed comprises more than 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Influenza vaccines remain the primary public health tool in reducing the ever-present burden of influenza and its complications. In seeking more immunogenic, more effective and more broadly cross-protective influenza vaccines, the landscape of influenza vaccines is rapidly expanding, both in near-term advances and next-generation vaccine design. Although the first influenza vaccines were licensed over 60 years ago, the hemagglutination-inhibition antibody titer is currently the only universally accepted immune correlate of protection against influenza. However, hemagglutination-inhibition titers appear to be less effective at predicting protection in populations at high risk for severe influenza disease; older adults, young children and those with certain medical conditions. The lack of knowledge and validated methods to measure alternate immune markers of protection against influenza remain a substantial barrier to the development of more immunogenic, broadly cross-reactive and effective influenza vaccines. Here, the authors review the knowledge of immune effectors of protection against influenza and discuss assessment methods for a broader range of immunological parameters that could be considered in the evaluation of traditional or new-generation influenza vaccines.
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