Biomedical subjects

Stephen C St Jeor

Publications and source records attributed to Stephen C St Jeor.

11 recordsLinked to original sources

PubMed2006

Human recombinant antimannan immunoglobulin G1 antibody confers resistance to hematogenously disseminated candidiasis in mice.

Mannan is a major cell wall component found in Candida species. Natural antimannan antibody is present in sera from most normal adults, but its role in host resistance to hematogenously disseminated candidiasis is unknown. The purpose of this study was to develop recombinant human antimannan antibody and to study its protective function. A phage Fab display combinatorial library containing Fab genes from bone marrow lymphocytes was screened with Candida albicans yeast cells and chemically purified mannan. One antimannan Fab, termed M1, was converted to a full-length immunoglobulin G1 antibody, M1g1, and M1g1 was produced in CHO cells. The M1g1 epitope was found in C. albicans serotypes A and B, Candida tropicalis, Candida guilliermondii, Candida glabrata, and Candida parapsilosis. Its expression was active at both 23 degrees C and 37 degrees C and uniform over the cell surface. BALB/c mice passively immunized with M1g1 were more resistant than control mice to a lethal hematogenous infection by C. albicans, as evidenced by extension of survival in an M1g1 dose-dependent manner (P, 0.08 to <0.001) and by reduction in number of infection foci and their size in the kidney. In vitro studies found that M1g1 promoted phagocytosis and phagocytic killing of C. albicans yeast cells by mouse peritoneal macrophages and was required for activation of the mouse complement cascade. Thus, human antimannan antibody may have a protective role in host resistance to systemic candidiasis.

Animals↗

PubMed2005

Replication and immunoactivity of the recombinant Peromyscus maniculatus cytomegalovirus expressing hantavirus G1 glycoprotein in vivo and in vitro.

Previously, we have shown that CMV isolated from deer mouse could be used in vivo and in vitro to express Sin Nombre virus (SNV) glycoprotein G1 in deer mice [Rizvanov AA, van Geelen AG, Morzunov S, et al. Generation of a recombinant cytomegalovirus for expression of a hantavirus glycoprotein. J.Virol. 2003;77(22):12203-10]. In this report, we further characterize replication of wild-type (wt) and recombinant Peromyscus CMV (PCMV) in vivo and in vitro using realtime PCR, and infectious center assays. Our findings indicate that both wt PCMV and recombinant PCMV establish persistent infections in P. maniculatus. In addition, we demonstrated that gamma irradiation of PCMV infected mice resulted in reactivation of recombinant PCMV in persistently infected mice.

Animals↗

PubMed2005

Interactions and trafficking of Andes and Sin Nombre Hantavirus glycoproteins G1 and G2.

This study was designed to investigate the trafficking of Andes virus (ANDV) and Sin Nombre virus (SNV) glycoproteins and to determine if ANDV or SNV glycoproteins G1 and G2 could be substituted for each other while still retaining normal trafficking. Trafficking of Hantaan virus (HNTV) and SNV glycoproteins has been studied and conflicting results were published regarding the Golgi targeting of G1 and G2 when expressed individually. The results reported in this manuscript suggest that both SNV and ANDV G1 and G2 expressed together, either from a single glycoprotein precursor (GPC) or from separate cDNAs, co-localize to the Golgi complex (GC). When expressed individually, neither G1 nor G2 was able to translocate from the endoplasmic reticulum (ER) to the GC. Interestingly, when ANDV G1 and SNV G2 or ANDV G2 and SNV G1 are co-expressed, they interact and are colocalized in the GC.

Animals↗

PubMed2005

Andes virus stimulates interferon-inducible MxA protein expression in endothelial cells.

MxA is a cellular protein activated in cells treated with type I interferons. MxA protein is a member of the dynamin superfamily of large guanosine triphosphatases. A unique property of Mx1 GTPases is their antiviral activity against a wide range of RNA viruses. Replication of several hantavirus strains is inhibited in cells constitutively expressing MxA protein. We have found that Andes virus (ANDV) infection up regulates transcription of MxA RNA and expression of MxA protein in human endothelial cells in vitro. Activation of MxA gene expression requires virus replication. Up-regulation of MxA gene expression in hantavirus infected cells varies depending on the cell type. The degree of activation of MxA gene expression is inversely correlated with the efficiency of hantavirus replication. Additionally, MxA protein is co-localized with hantavirus nucleocapsid protein in infected cell. Our data suggest that MxA by interacting with the virus nucleocapsid protein inhibits production of new infectious virus particles.

Animals↗

PubMed2005

Hantaviruses: molecular biology, evolution and pathogenesis.

Hantaviruses are tri-segmented negative sense single stranded RNA viruses that belong to the family Bunyaviridae. In nature, hantaviruses are exclusively maintained in the populations of their specific rodent hosts. In their natural host species, hantaviruses usually develop a persistent infection with prolonged virus shedding in excreta. Humans become infected by inhaling virus contaminated aerosol. Unlike asymptomatic infection in rodents, hantaviruses cause two acute febrile diseases in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The mortality rate varies from 0.1% to 40% depending on the virus involved. Hantaviruses are distributed world wide, with over 150,000 HFRS and HPS cases being registered annually. In this review we summarize current knowledge on hantavirus molecular biology, epidemiology, genetic diversity and co-evolution with rodent hosts. In addition, special attention was given in this review to describing clinical manifestation of HFRS and HPS, and advances in our current understanding of the host immune response, treatment, and prevention.

Animals↗

PubMed2004

Three-week incubation period for hantavirus infection.

Occasionally a case report can provide enormous insight into the pathogenesis of an infectious disease. In this instance, 2 Iowa boys were bitten by the same mouse on May 1, 1999. Three weeks later, both boys developed sin nombre hantavirus pulmonary syndrome. Thus, the incubation period of hantavirus infection has been documented. Both survived; one of the 2 boys continued to have a very high titer of hantavirus antibody 4 years after the mouse bite.

Adolescent↗

PubMed2003

Generation of a recombinant cytomegalovirus for expression of a hantavirus glycoprotein.

A cytomegalovirus (CMV) was isolated from its natural host, Peromyscus maniculatus, and was designated Peromyscus CMV (PCMV). A recombinant PCMV was constructed that contained Sin Nombre virus glycoprotein G1 (SNV-G1) fused in frame to the enhanced green fluorescent protein (EGFP) gene inserted into a site homologous to the human CMV UL33 (P33) gene. The recombinant CMV was used for expression and immunization of deer mice against SNV-G1. The results of the study indicate that P. maniculatus could be infected with as few as 10 virus particles of recombinant virus. Challenge of P. maniculatus with either recombinant or wild-type PCMV produced no overt pathology in infected animals. P. maniculatus immunized with recombinant virus developed an antibody response to SNV and EGFP. When rechallenged with recombinant virus, animals exhibited an anamnestic response against SNV. Interestingly, a preexisting immune response against PCMV did not prevent reinfection with recombinant PCMV.

Amino Acid Sequence↗

PubMed2002

Complete nucleotide sequence of a Chilean hantavirus.

We have determined the genomic sequence of an Andes virus (ANDV) strain isolated from an infected Oligoryzomys longicaudatus rodent trapped in Chile in 1997. This strain, for which we propose the designation Chile R123, reproduces essential attributes of hantavirus pulmonary syndrome (HPS) when injected intramuscularly into laboratory hamsters (Hooper et al., Virology 289 (2001) 6-14). The L, M, and S segment sequences of Chile R123 are 6562, 3671, and 1871 nt long, respectively, with an overall G+C content of 38.5%. These respective genome segments could encode a 247 kd RNA-dependent RNA polymerase (RdRP), 126 kd glycoprotein precursor (GPC), and 48 kd nucleocapsid (N) protein, in line with other Sigmodontine rodent-associated hantaviruses. Among hantaviruses for which complete genomic sequences are available, Chile R123 is most closely related to Sin Nombre virus (SNV) strain NM R11, with greater than 85% amino acid identity between translated L and S segments and 78% amino acid identity between translated M segments. Because Chile R123 shares essentially 100% amino acid identity in regions of overlap with partially sequenced Argentinian and Chilean ANDV strains, Syrian hamster pathogenicity and the potential for interhuman transmission are features likely common to all ANDV strains.

Animals↗

PubMed2002

Hantavirus immunology.

Two clinical syndromes are associated with hantavirus infection in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Autopsy findings typically reveal a common feature of increased permeability in microvascular beds, suggesting vascular endothelium is a prime target for virus infection. Endothelial cells are susceptible to hantavirus infection; however, virus does not cause cytopathic effects, to explain increased endothelium permeability. Therefore, immune mechanisms were suggested to play a crucial role in hantavirus pathogenesis. In this review, we summarize data on hantavirus-induced immune disturbances and discuss their implication in capillary leakage caused by hantavirus infection.

Endothelium, Vascular↗

PubMed2002

Analysis of hantavirus genetic diversity in Argentina: S segment-derived phylogeny.

Nucleotide sequences were determined for the complete S genome segments of the six distinct hantavirus genotypes from Argentina and for two cell culture-isolated Andes virus strains from Chile. Phylogenetic analysis indicates that, although divergent from each other, all Argentinian hantavirus genotypes group together and form a novel phylogenetic clade with the Andes virus. The previously characterized South American hantaviruses Laguna Negra virus and Rio Mamore virus make up another clade that originates from the same ancestral node as the Argentinian/Chilean viruses. Within the clade of Argentinian/Chilean viruses, three subclades can be defined, although the branching order is somewhat obscure. These are made of (i) "Lechiguanas-like" virus genotypes, (ii) Maciel virus and Pergamino virus genotypes, and (iii) strains of the Andes virus. Two hantavirus genotypes from Brazil, Araraquara and Castello dos Sonhos, were found to group with Maciel virus and Andes virus, respectively. The nucleocapsid protein amino acid sequence variability among the members of the Argentinian/Chilean clade does not exceed 5.8%. It is especially low (3.5%) among oryzomyine species-associated virus genotypes, suggesting recent divergence from the common ancestor. Interestingly, the Maciel and Pergamino viruses fit well with the rest of the clade although their hosts are akodontine rodents. Taken together, these data suggest that under conditions in which potential hosts display a high level of genetic diversity and are sympatric, host switching may play a prominent role in establishing hantavirus genetic diversity. However, cospeciation still remains the dominant factor in the evolution of hantaviruses.

Animals↗

PubMed2002

Infection dynamics of Sin Nombre virus after a widespread decline in host populations.

Many researchers have speculated that infection dynamics of Sin Nombre virus are driven by density patterns of its major host, Peromyscus maniculatus. Few, if any, studies have examined this question systematically at a realistically large spatial scale, however. We collected data from 159 independent field sites within a 1 million-hectare study area in Nevada and California, from 1995-1998. In 1997, there was a widespread and substantial reduction in host density. This reduction in host density did not reduce seroprevalence of antibody to Sin Nombre virus within host populations. During this period, however, there was a significant reduction in the likelihood that antibody-positive mice had detectable virus in their blood, as determined by reverse-transcriptase polymerase chain reaction. Our findings suggest 2 possible causal mechanisms for this reduction: an apparent change in the age structure of host populations and landscape-scale patterns of host density. This study indicates that a relationship does exist between host density and infection dynamics and that this relationship concurrently operates at different spatial scales. It also highlights the limitations of antibody seroprevalence as a metric of infections, especially during transient host-density fluctuations.

Animals↗