The structure of the hantavirus zinc finger domain is conserved and represents the only natively folded region of the Gn cytoplasmic tail

Hantaviruses, of the family Bunyaviridae, are present throughout the world and cause a variety of infections ranging from the asymptomatic to mild and severe hemorrhagic fevers. Hantaviruses are enveloped anti-sense RNA viruses that contain three genomic segments that encode for a nucleocapsid protein, two membrane glycoproteins (Gn and Gc), and an RNA polymerase. Recently, the pathogenicity of hantaviruses has been mapped to the carboxyl end of the 150 residue Gn cytoplasmic tail. The Gn tail has also been shown to play a role in binding the ribonucleoprotein (RNP), a step critical for virus assembly. In this study, we use NMR spectroscopy to compare the structure of a Gn tail zinc finger domain of both a pathogenic (Andes) and a non-pathogenic (Prospect Hill) hantavirus. We demonstrate that despite a stark difference in the virulence of both of these viruses, the structure of the Gn core zinc finger domain is largely conserved in both strains. We also use NMR backbone relaxation studies to demonstrate that the regions of the Andes virus Gn tail immediately outside the zinc finger domain, sites known to bind the RNP, are disordered and flexible, thus intimating that the zinc finger domain is the only structured region of the Gn tail. These structural observations provide further insight into the role of the Gn tail during viral assembly as well as its role in pathogenesis

Hantavirus infection in humans and rodents, northwestern Argentina

We initiated a study to elucidate the ecology and epidemiology of hantavirus infections in northern Argentina. The northwestern hantavirus pulmonary syndrome (HPS)–endemic area of Argentina comprises Salta and Jujuy Provinces. Between 1997 and 2000, 30 HPS cases were diagnosed in Jujuy Province (population 512,329). Most patients had a mild clinical course, and the death rate (13.3%) was low. We performed a serologic and epidemiologic survey in residents of the area, in conjunction with a serologic study in rodents. The prevalence of hantavirus antibodies in the general human population was 6.5%, one of the highest reported in the literature. No evidence of interhuman transmission was found, and the high preva-lence of hantavirus antibody seemed to be associated with the high infestation of rodents detected in domestic and peridomestic habitats.Fil: Pini, Noemi. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Levis, Silvana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Calderón, Gladys. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Ramirez, Josefina. Hospital San Miguel; Argentina.Fil: Bravo, Daniel. Hospital Oscar Orias; Argentina.Fil: Lozano, Elena. Hospital San Miguel; Argentina.Fil: Ripoll, Carlos. Dirección de Epidemiología; Argentina.Fil: St. Jeor, Stephen. University of Nevada; Estados Unidos.Fil: Ksiazek, Thomas G. Centers for Disease Control and Prevention; Estados Unidos.Fil: Barquez, Rubén. Universidad Nacional de Tucumán; Argentina.Fil: Enria, Delia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina

Hantavirus Infection in Humans and Rodents, Northwestern Argentina

We initiated a study to elucidate the ecology and epidemiology of hantavirus infections in northern Argentina. The northwestern hantavirus pulmonary syndrome (HPS)–endemic area of Argentina comprises Salta and Jujuy Provinces. Between 1997 and 2000, 30 HPS cases were diagnosed in Jujuy Province (population 512,329). Most patients had a mild clinical course, and the death rate (13.3%) was low. We performed a serologic and epidemiologic survey in residents of the area, in conjunction with a serologic study in rodents. The prevalence of hantavirus antibodies in the general human population was 6.5%, one of the highest reported in the literature. No evidence of interhuman transmission was found, and the high prevalence of hantavirus antibody seemed to be associated with the high infestation of rodents detected in domestic and peridomestic habitats

Hantavirus infection in humans and rodents, northwestern Argentina

We initiated a study to elucidate the ecology and epidemiology of hantavirus infections in northern Argentina. The northwestern hantavirus pulmonary syndrome (HPS)–endemic area of Argentina comprises Salta and Jujuy Provinces. Between 1997 and 2000, 30 HPS cases were diagnosed in Jujuy Province (population 512,329). Most patients had a mild clinical course, and the death rate (13.3%) was low. We performed a serologic and epidemiologic survey in residents of the area, in conjunction with a serologic study in rodents. The prevalence of hantavirus antibodies in the general human population was 6.5%, one of the highest reported in the literature. No evidence of interhuman transmission was found, and the high preva-lence of hantavirus antibody seemed to be associated with the high infestation of rodents detected in domestic and peridomestic habitats.Fil: Pini, Noemi. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Levis, Silvana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Calderón, Gladys. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Ramirez, Josefina. Hospital San Miguel; Argentina.Fil: Bravo, Daniel. Hospital Oscar Orias; Argentina.Fil: Lozano, Elena. Hospital San Miguel; Argentina.Fil: Ripoll, Carlos. Dirección de Epidemiología; Argentina.Fil: St. Jeor, Stephen. University of Nevada; Estados Unidos.Fil: Ksiazek, Thomas G. Centers for Disease Control and Prevention; Estados Unidos.Fil: Barquez, Rubén. Universidad Nacional de Tucumán; Argentina.Fil: Enria, Delia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina

Coexistence of Several Novel Hantaviruses in Rodents Indigenous to North America

AbstractThree genetically distinct members of the Hantavirus genus have been detected in Nevada rodents by RT-PCR and nucleotide sequence analysis. These include Sin Nombre (SN), El Moro Canyon (ELMC), and Prospect Hill (PH)-like viruses which are primarily associated with Peromyscus maniculatus (deer mouse), Reithrodontomys megalotis (western harvest mouse), and Microtus spp. (voles), respectively. Although this region of the United States is ecologically diverse, rodents infected with different hantaviruses appear to coexist in several different geographical and ecological zones. In two widely separated states, Nevada and North Dakota, PH-like viruses are present in three different species of vole. In addition, ELMC-like virus has been detected in both R. megalotis and M. montanus (mountain vole). SN virus is a cause of hantavirus pulmonary syndrome throughout much of the United States. SN virus RNA is found in 12.5% of P. maniculatus in Nevada and eastern California. Two lineages of SN virus coexist in this region and differ from SN viruses originally found in infected rodents in New Mexico, Arizona, and Colorado. These data show the complexity of hantavirus maintenance in rodents. Distinct hantaviruses or virus lineages can coexist either in different or the same rodent species and in either different or tile same geographic or ecological zones

Hantavirus pulmonary syndrome in northwestern Argentina : circulation of Laguna Negra virus associated with Calomys callosus

The purpose of this study was to characterize the hantaviruses circulating in northwestern Argentina. Human and rodent studies were conducted in Yuto, where most cases of hantavirus pulmonary syndrome (HPS) occur. Partial virus genome sequences were obtained from the blood of 12 cases of HPS, and from the lungs of 4 Calomys callosus and 1 Akodon simulator. Phylogenetic analysis showed that three genotypes associated with HPS circulate in Yuto. Laguna Negra (LN) virus, associated with C. laucha in Paraguay, was identified for the first time in Argentina; it was recovered from human cases and from C. callosus samples. The high sequence identity between human and rodent samples implicated C. callosus as the primary rodent reservoir for LN virus in Yuto. The genetic analysis showed that the Argentinian LN virus variant differed 16.8% at the nucleotide level and 2.9% at the protein level relative to the Paraguayan LN virus. The other two hantavirus lineages identified were the previously known Bermejo and Orán viruses.Fil: Levis, Silvana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Garcia, Jorge. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Pini, Noemí. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Calderón, Gladys. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Ramírez, Josefina. Hospital San Miguel; Argentina.Fil: Bravo, Daniel. Hospital Oscar Orías; Argentina.Fil: St. Jeor, Stephen. University of Nevada. Department of Microbiology; Estados Unidos.Fil: Ripoll, Carlos. Dirección de Epidemiología. San Salvador de Jujuy, Jujuy; Argentina.Fil: Bego, Mariana. University of Nevada. Department of Microbiology; Estados Unidos.Fil: Lozano, Elena. Hospital San Miguel; Argentina.Fil: Barquez, Rubén. Fundación Miguel Lillo; Argentina.Fil: Ksiazek, Thomas G. Centers for Disease Control and Prevention. Special Pathogens Branch; Estados Unidos.Fil: Enria, Delia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina

Sin Nombre Virus and Rodent Species Diversity: A Test of the Dilution and Amplification Hypotheses

BACKGROUND:Species diversity is proposed to greatly impact the prevalence of pathogens. Two predominant hypotheses, the "Dilution Effect" and the "Amplification Effect", predict divergent outcomes with respect to the impact of species diversity. The Dilution Effect predicts that pathogen prevalence will be negatively correlated with increased species diversity, while the Amplification Effect predicts that pathogen prevalence will be positively correlated with diversity. For many host-pathogen systems, the relationship between diversity and pathogen prevalence has not be empirically examined. METHODOLOGY/PRINCIPAL FINDINGS:We tested the Dilution and Amplification Effect hypotheses by examining the prevalence of Sin Nombre virus (SNV) with respect to diversity of the nocturnal rodent community. SNV is directly transmitted primarily between deer mice (Peromyscus maniculatus). Using mark-recapture sampling in the Spring and Fall of 2003-2005, we measured SNV prevalence in deer mice at 16 landscape level sites (3.1 hectares each) that varied in rodent species diversity. We explored several mechanisms by which species diversity may affect SNV prevalence, including reduced host density, reduced host persistence, the presence of secondary reservoirs and community composition. We found a negative relationship between species diversity and SNV prevalence in deer mice, thereby supporting the Dilution Effect hypothesis. Deer mouse density and persistence were lower at sites with greater species diversity; however, only deer mouse persistence was positively correlated with SNV prevalence. Pinyon mice (P. truei) may serve as dilution agents, having a negative effect on prevalence, while kangaroo rats (Dipodomys ordii), may have a positive effect on the prevalence of SNV, perhaps through effects on deer mouse behavior. CONCLUSIONS/SIGNIFICANCE:While previous studies on host-pathogen systems have found patterns of diversity consistent with either the Dilution or Amplification Effects, the mechanisms by which species diversity influences prevalence have not been investigated. Our study indicates that changes in host persistence, coupled with interspecific interactions, are important mechanisms through which diversity may influence patterns of pathogens. Our results reveal the complexity of rodent community interactions with respect to SNV dynamics

Modulation of Human Mesenchymal Stem Cell Immunogenicity through Forced Expression of Human Cytomegalovirus US Proteins

BACKGROUND: Mesenchymal stem cells (MSC) are promising candidates for cell therapy, as they migrate to areas of injury, differentiate into a broad range of specialized cells, and have immunomodulatory properties. However, MSC are not invisible to the recipient's immune system, and upon in vivo administration, allogeneic MSC are able to trigger immune responses, resulting in rejection of the transplanted cells, precluding their full therapeutic potential. Human cytomegalovirus (HCMV) has developed several strategies to evade cytotoxic T lymphocyte (CTL) and Natural Killer (NK) cell recognition. Our goal is to exploit HCMV immunological evasion strategies to reduce MSC immunogenicity. METHODOLOGY/PRINCIPAL FINDINGS: We genetically engineered human MSC to express HCMV proteins known to downregulate HLA-I expression, and investigated whether modified MSC were protected from CTL and NK attack. Flow cytometric analysis showed that amongst the US proteins tested, US6 and US11 efficiently reduced MSC HLA-I expression, and mixed lymphocyte reaction demonstrated a corresponding decrease in human and sheep mononuclear cell proliferation. NK killing assays showed that the decrease in HLA-I expression did not result in increased NK cytotoxicity, and that at certain NK∶MSC ratios, US11 conferred protection from NK cytotoxic effects. Transplantation of MSC-US6 or MSC-US11 into pre-immune fetal sheep resulted in increased liver engraftment when compared to control MSC, as demonstrated by qPCR and immunofluorescence analyses. CONCLUSIONS AND SIGNIFICANCE: These data demonstrate that engineering MSC to express US6 and US11 can be used as a means of decreasing recognition of MSC by the immune system, allowing higher levels of engraftment in an allogeneic transplantation setting. Since one of the major factors responsible for the failure of allogeneic-donor MSC to engraft is the mismatch of HLA-I molecules between the donor and the recipient, MSC-US6 and MSC-US11 could constitute an off-the-shelf product to overcome donor-recipient HLA-I mismatch

Stephen de St. Jeor 1962

Student field notes from zoology classes in 196