Hantaviruses: a global disease problem.

Hantaviruses are carried by numerous rodent species throughout the world. In 1993, a previously unknown group of hantaviruses emerged in the United States as the cause of an acute respiratory disease now termed hantavirus pulmonary syndrome (HPS). Before than, hantaviruses were known as the etiologic agents of hemorrhagic fever with renal syndrome, a disease that occurs almost entirely in the Eastern Hemisphere. Since the discovery of the HPS-causing hantaviruses, intense investigation of the ecology and epidemiology of hantaviruses has led to the discovery of many other novel hantaviruses. Their ubiquity and potential for causing severe human illness make these viruses an important public health concern; we reviewed the distribution, ecology, disease potential, and genetic spectrum

Spatio-temporal patterns in the Hantavirus infection

We present a model of the infection of Hantavirus in deer mouse, Peromyscus maniculatus, based on biological observations of the system in the North American Southwest. The results of the analysis shed light on relevant observations of the biological system, such as the sporadical disappearance of the infection, and the existence of foci or ``refugia'' that perform as reservoirs of the virus when environmental conditions are less than optimal.Comment: 6 pages, 5 inlined figures, RevTeX 4 forma

An immunoinformatics-derived DNA vaccine encoding human class II T cell epitopes of Ebola virus, Sudan virus, and Venezuelan equine encephalitis virus is immunogenic in HLA transgenic mice

Immunoinformatics tools were used to predict human leukocyte antigen (HLA) class II-restricted T cell epitopes within the envelope glycoproteins and nucleocapsid proteins of Ebola virus (EBOV) and Sudan virus (SUDV) and the structural proteins of Venezuelan equine encephalitis virus (VEEV). Selected epitopes were tested for binding to soluble HLA molecules representing 5 class II alleles (DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, and DRB1*1501). All but one of the 25 tested peptides bound to at least one of the DRB1 alleles, and 4 of the peptides bound at least moderately or weakly to all 5 DRB1 alleles. Additional algorithms were used to design a single “string-of-beads” expression construct with 44 selected epitopes arranged to avoid creation of spurious junctional epitopes. Seventeen of these 44 predicted epitopes were conserved between the major histocompatibility complex (MHC) of humans and mice, allowing initial testing in mice. BALB/c mice vaccinated with the multi-epitope construct developed statistically significant cellular immune responses to EBOV, SUDV, and VEEV peptides as measured by interferon (IFN)-γ ELISpot assays. Significant levels of antibodies to VEEV, but not EBOV, were also detected in vaccinated BALB/c mice. To assess immunogenicity in the context of a human MHC, HLA-DR3 transgenic mice were vaccinated with the multi-epitope construct and boosted with a mixture of the 25 peptides used in the binding assays. The vaccinated HLA-DR3 mice developed significant cellular immune responses to 4 of the 25 (16%) tested individual class II peptides as measured by IFN-γ ELISpot assays. In addition, these mice developed antibodies against EBOV and VEEV as measured by ELISA. While a low but significant level of protection was observed in vaccinated transgenic mice after aerosol exposure to VEEV, no protection was observed after intraperitoneal challenge with mouse-adapted EBOV. These studies provide proof of concept for the use of an informatics approach to design a multi-agent, multi-epitope immunogen and provide a basis for further testing aimed at focusing immune responses toward desired protective T cell epitopes

Puumala hantavirus Infection in Humans and in the Reservoir Host, Ardennes Region, France

We compared the occurrence of nephropathia epidemica cases, over a multi-annual population cycle, in northeastern France with the hantavirus serology for bank voles captured in the same area. We discuss hypotheses to explain the pattern of infection in both humans and rodents and their synchrony

Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine

Puumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact is considerable. There is no licensed vaccine or specific therapeutic to prevent or treat HFRS. Here we report the synthesis of a codon-optimized, full-lengthMsegment open reading frame and its cloning into a DNA vaccine vector to produce the plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer neutralizing antibodies in hamsters and nonhuman primates. Vaccination with pWRG/ PUU-M(s2) protected hamsters against infection with PUUV but not against infection by related HFRS-associated hantaviruses. Unexpectedly, vaccination protected hamsters in a lethal disease model of Andes virus (ANDV) in the absence of ANDV crossneutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model

The VirusBanker database uses a Java program to allow flexible searching through Bunyaviridae sequences

<p>Abstract</p> <p>Background</p> <p>Viruses of the <it>Bunyaviridae </it>have segmented negative-stranded RNA genomes and several of them cause significant disease. Many partial sequences have been obtained from the segments so that GenBank searches give complex results. Sequence databases usually use HTML pages to mediate remote sorting, but this approach can be limiting and may discourage a user from exploring a database.</p> <p>Results</p> <p>The VirusBanker database contains <it>Bunyaviridae </it>sequences and alignments and is presented as two spreadsheets generated by a Java program that interacts with a MySQL database on a server. Sequences are displayed in rows and may be sorted using information that is displayed in columns and includes data relating to the segment, gene, protein, species, strain, sequence length, terminal sequence and date and country of isolation. <it>Bunyaviridae </it>sequences and alignments may be downloaded from the second spreadsheet with titles defined by the user from the columns, or viewed when passed directly to the sequence editor, Jalview.</p> <p>Conclusion</p> <p>VirusBanker allows large datasets of aligned nucleotide and protein sequences from the <it>Bunyaviridae </it>to be compiled and winnowed rapidly using criteria that are formulated heuristically.</p

Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine

Puumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact is considerable. There is no licensed vaccine or specific therapeutic to prevent or treat HFRS. Here we report the synthesis of a codon-optimized, full-lengthMsegment open reading frame and its cloning into a DNA vaccine vector to produce the plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer neutralizing antibodies in hamsters and nonhuman primates. Vaccination with pWRG/ PUU-M(s2) protected hamsters against infection with PUUV but not against infection by related HFRS-associated hantaviruses. Unexpectedly, vaccination protected hamsters in a lethal disease model of Andes virus (ANDV) in the absence of ANDV crossneutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model

Genetic diversity and distribution of Peromyscus-borne hantaviruses in North America.

The 1993 outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States was associated with Sin Nombre virus, a rodent-borne hantavirus; The virus' primary reservoir is the deer mouse (Peromyscus maniculatus). Hantavirus-infected rodents were identified in various regions of North America. An extensive nucleotide sequence database of an 139 bp fragment amplified from virus M genomic segments was generated. Phylogenetic analysis confirmed that SNV-like hantaviruses are widely distributed in Peromyscus species rodents throughout North America. Classic SNV is the major cause of HPS in North America, but other Peromyscine-borne hantaviruses, e.g., New York and Monongahela viruses, are also associated with HPS cases. Although genetically diverse, SNV-like viruses have slowly coevolved with their rodent hosts. We show that the genetic relationships of hantaviruses in the Americas are complex, most likely as a result of the rapid radiation and speciation of New World sigmodontine rodents and occasional virus-host switching events