Parenteral Transmission of the Novel Human Parvovirus PARV4

Transmission routes of PARV4, a newly discovered human parvovirus, were investigated by determining frequencies of persistent infections using autopsy samples from different risk groups. Predominantly parenteral routes of transmission were demonstrated by infection restricted to injection drug users and persons with hemophilia and absence of infection in homosexual men with AIDS and low-risk controls

Functional and Immunological Relevance of Anaplasma marginale Major Surface Protein 1a Sequence and Structural Analysis.

Bovine anaplasmosis is caused by cattle infection with the tick-borne bacterium, Anaplasma marginale. The major surface protein 1a (MSP1a) has been used as a genetic marker for identifying A. marginale strains based on N-terminal tandem repeats and a 5'-UTR microsatellite located in the msp1a gene. The MSP1a tandem repeats contain immune relevant elements and functional domains that bind to bovine erythrocytes and tick cells, thus providing information about the evolution of host-pathogen and vector-pathogen interactions. Here we propose one nomenclature for A. marginale strain classification based on MSP1a. All tandem repeats among A. marginale strains were classified and the amino acid variability/frequency in each position was determined. The sequence variation at immunodominant B cell epitopes was determined and the secondary (2D) structure of the tandem repeats was modeled. A total of 224 different strains of A. marginale were classified, showing 11 genotypes based on the 5'-UTR microsatellite and 193 different tandem repeats with high amino acid variability per position. Our results showed phylogenetic correlation between MSP1a sequence, secondary structure, B-cell epitope composition and tick transmissibility of A. marginale strains. The analysis of MSP1a sequences provides relevant information about the biology of A. marginale to design vaccines with a cross-protective capacity based on MSP1a B-cell epitopes

Changes in putative 2D structure and disorder analysis of A. marginale MSP1a tandem repeats.

<p>The PSIPRED web server was used to predict the 2D structure. The tandem repeats were grouped into fourteen 2D structure models. Tandem repeats shown represent prototypes of corresponding tandem repeat 2D structures. The second column shows (model presented) the ID of the tandem repeat presented as prototype. Models ID in red represent tandem repeats in R1 position (first tandem in the MSP1a sequence).</p

Effect of putative MSP1a tandem repeat 2-D structure on A. marginale tick transmission phenotype.

<p>The information about transmission of A. marginale strains by ticks was collected from (*) de la Fuente et al. (2003) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065243#pone.0065243-delaFuente2" target="_blank">[10]</a>,</p><p>(**) Zivkovic et al. (2007) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065243#pone.0065243-Zivkovic1" target="_blank">[65]</a>,</p><p>(***) Futse et al. (2003) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065243#pone.0065243-Futse2" target="_blank">[44]</a>,</p><p>(****) Shkap et al. 2009 (****) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065243#pone.0065243-Shkap1" target="_blank">[39]</a>,</p><p>(−) Leverich et al. (2008) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065243#pone.0065243-Leverich1" target="_blank">[66]</a>, and (+) Barbet et al (2001) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065243#pone.0065243-Barbet3" target="_blank">[67]</a>.</p><p>TCE-binding tandem repeats are underlined. Abbreviation: ND, not determined.</p

MSP1a tandem repeat sequences in A. marginale strains.

<p>The one letter amino acid code was used to depict MSP1a repeat sequences. Dots indicate identical amino acids and gaps indicate deletion/insertions. The ID of each repeat form was given following the nomenclature proposed by de la Fuente et al. (2007) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065243#pone.0065243-delaFuente4" target="_blank">[14]</a>. The sequences from 114 until 161 are the newly classified.</p

World A. marginale MSP1a molecular map.

<p>The worldwide molecular characterization of A. marginale MSP1a sequences is shown. The number of A. marginale strains (S), tandem repeats (TR), tandem repeat 2D structures (TR-2D), functional tandem repeats (FTR) containing D and E at position 20 and B cell epitope types (BCE) and microsatellites (MS) are represented for each country. Primary data is depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065243#pone-0065243-g001" target="_blank">figures 1</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065243#pone-0065243-g003" target="_blank">3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065243#pone-0065243-g006" target="_blank">6</a>. The information on 5′ UTR microsatellites is not available (NA) for some sequences.</p

Geographical occurrence of the most common <i>A. marginale</i> strains.

<p>The most frequent A. marginale strains and their geographical occurrence are shown. The most common tandem repeats found among all the A. marginale strains are underlined and there were found more than 60 (<b><u>M</u></b>), 80 (<b><u>β</u></b>) and 90 (<b><u>B</u></b>) times.</p

B-cell epitope analysis in A. marginale MSP1a tandem repeats.

<p>The B-cell epitopes were predicted using BCPRED server. The type 1 B-cell epitope was used as reference (Model) for comparisons. (A) Clustalw alignment and amino acid changes in the 5 more represented MSP1a tandem repeat B cell epitopes. B-cell epitope types model (light violet), 1 (blue), 10 (yellow), 11 (dark violet) and 17 (red) are shown. (B) Percent of tandem repeats containing each type of B cell epitopes. (C) Neighbor joining phylogenetic tree based on B cell epitope amino acid sequences showing the two clusters formed by the 5 more represented B cell epitopes. Cluster-1: Types 1 and 11 and Cluster-2: Types Model, 10 and 17. Correlations between VaxiJen/Blastp (D), BCPRED/Blastp scores (E) and VaxiJen/BCPRED (F) scores are shown. These correlations suggest that the epitopes with higher homology (Blastp score) share in common the immunogenic properties represented by VaxiJen/BCPRED.</p