Location and primary structure of a major antigenic site for poliovirus neutralization

We have determined a major antigenic site for virus neutralization on the capsid protein VP1 of poliovirus type 3. Antigenic mutant viruses selected for resistance to individual monoclonal antibodies had point mutations concentrated in a region 277-294 bases downstream from the start of the region of viral RNA coding for VP1. These findings provide the basis for an improved understanding of the molecular basis of virus neutralization.     

Antigen chimaeras of poliovirus as potential new vaccines

Polioviruses occur as three distinct serotypes, 1, 2 and 3, and are composed of a single-stranded positive-sense RNA genome of approximately 7,450 nucleotides enclosed in an icosahedral particle of diameter 27 nm. The three-dimensional crystallographic structure of poliovirus type 1 has been determined at 2.9 A resolution, providing a detailed knowledge of the folding and arrangement of the individual virus proteins, VP1-VP4. From this and the characterization of monoclonal antibody-resistant mutants, the amino acids contributing to antigenic sites have been identified and located on the surface of the virus particle. Here we describe the construction and characterization of a poliovirus chimaera having a defined region of type 3 inserted into type 1. This virus has composite antigenicity and the substitute site is immunogenic in small animals and primates. The ability to construct such viruses has implications for the design of improved poliovirus vaccine strains or vaccines against other picornaviruses, such as hepatitis A.     

An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies

The Sabin type 1 vaccine strain of poliovirus is probably the safest and most successful live-attenuated vaccine virus used in humans. Its widespread use since the early 1960s has contributed significantly to the virtual eradication of poliomyelitis in developed countries. We have reported previously the construction of an intertypic antigen chimaera of poliovirus, based on the Sabin 1 strain, and proposed that this virus could be modified to express on its surface antigenic determinants from other pathogens. We describe here the construction and characterization of a poliovirus antigen chimaera containing an epitope from the transmembrane glycoprotein (gp41) of human immunodeficiency virus type 1 (HIV-1). In antibody absorption experiments, the virus chimaera inhibited neutralization of HIV-1 by antipeptide monoclonal antibodies specific for the gp41 epitope and significantly reduced the group specific neutralizing activity of HIV-1-positive human sera. Rabbit antisera raised by subcutaneous injection of the polio/HIV chimaera in adjuvant was shown to be specific for HIV-1 gp41 in peptide-binding assays and by western blotting. Moreover, the antisera neutralized a wide range of American and African HIV-1 isolates and also inhibited virus-induced cell fusion. Monoclonal antibodies against the HIV-1 derived regions of the chimaera also neutralized HIV-1. These results establish the potential of using poliovirus for the presentation of foreign antigens and suggest that Sabin 1 poliovirus/HIV chimaeras could offer an approach to the development of an HIV vaccine.     

Tree barks as a natural trap for airborne spores and pollen grains from China

The present article deals with the use of tree barks as a natural trap for airborne spores and pollen grains in China. The study carried out at the southern part of Beijing Botanical Garden, Institute of Botany, Chinese Academy of Sciences has yielded a variety of palynomorphs mostly belonging to tree taxa. New methodologies for extraction of palynomorphs from tree barks have been suggested. Bark samples were collected from three taxa, i.e., Paulownia fortunei Hemsl. （Scrophulariaceae）, Quercus dentata Thunb. （Fagaceae）, and Picea meyeri Rehder ＆ E.H. Wilson （Pinaceae） having different bark morphologies. P. fortunei with a comparatively soft and fissured bark is believed to have a greater potential for trapping airborne spores and pollen grains compared to the stiff and less fissured barks of Q. dentata and the scaly bark of P. meyeri. Old barks yield better data in terms of quantity and quality of trapped pollen and spores. The present study throws new light on the modern pollen rain, spore-pollen dispersal, and their deposition in and aroundBeijing Botanical Garden, and other different parts of China.     

Genome-wide association study identifies a common variant associated with risk of endometrial cancer

Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.     

Recent advances in the biosynthesis of modified tetrapyrroles: the discovery of an alternative pathway for the formation of heme and heme d 1

Hemes (a, b, c, and o) and heme d ₁ belong to the group of modified tetrapyrroles, which also includes chlorophylls, cobalamins, coenzyme F₄₃₀, and siroheme. These compounds are found throughout all domains of life and are involved in a variety of essential biological processes ranging from photosynthesis to methanogenesis. The biosynthesis of heme b has been well studied in many organisms, but in sulfate-reducing bacteria and archaea, the pathway has remained a mystery, as many of the enzymes involved in these characterized steps are absent. The heme pathway in most organisms proceeds from the cyclic precursor of all modified tetrapyrroles uroporphyrinogen III, to coproporphyrinogen III, which is followed by oxidation of the ring and finally iron insertion. Sulfate-reducing bacteria and some archaea lack the genetic information necessary to convert uroporphyrinogen III to heme along the “classical” route and instead use an “alternative” pathway. Biosynthesis of the isobacteriochlorin heme d ₁, a cofactor of the dissimilatory nitrite reductase cytochrome cd ₁, has also been a subject of much research, although the biosynthetic pathway and its intermediates have evaded discovery for quite some time. This review focuses on the recent advances in the understanding of these two pathways and their surprisingly close relationship via the unlikely intermediate siroheme, which is also a cofactor of sulfite and nitrite reductases in many organisms. The evolutionary questions raised by this discovery will also be discussed along with the potential regulation required by organisms with overlapping tetrapyrrole biosynthesis pathways.     

Strategies for containing an emerging influenza pandemic in Southeast Asia

Highly pathogenic H5N1 influenza A viruses are now endemic in avian populations in Southeast Asia, and human cases continue to accumulate. Although currently incapable of sustained human-to-human transmission, H5N1 represents a serious pandemic threat owing to the risk of a mutation or reassortment generating a virus with increased transmissibility. Identifying public health interventions that might be able to halt a pandemic in its earliest stages is therefore a priority. Here we use a simulation model of influenza transmission in Southeast Asia to evaluate the potential effectiveness of targeted mass prophylactic use of antiviral drugs as a containment strategy. Other interventions aimed at reducing population contact rates are also examined as reinforcements to an antiviral-based containment policy. We show that elimination of a nascent pandemic may be feasible using a combination of geographically targeted prophylaxis and social distancing measures, if the basic reproduction number of the new virus is below 1.8. We predict that a stockpile of 3 million courses of antiviral drugs should be sufficient for elimination. Policy effectiveness depends critically on how quickly clinical cases are diagnosed and the speed with which antiviral drugs can be distributed.