Dominant Glycoprotein Epitope of Four Corners Hantavirus is Conserved Across a Wide Geographical Area

Abstract

A newly identified hantavirus, tentatively called Four Corners virus (FCV), was found to be the aetiological agent of a 1993 outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States. Immunodominant epitopes of 43 and 31 amino acids were identified in the nucleocapsid protein and G1 glycoprotein, respectively. The G1 genes of different hantaviruses are highly divergent, suggesting that geographically diverse FCVs might fail to cross-react owing to antigenic drift. We now show that the immunodominant epitope of G1 is conserved among 18 FCVs from a broad geographical area, despite extensive nucleotide sequence heterogeneity. Antibodies from all 45 HPS patients, separated by more than 3000 km were shown to be reactive with the dominant G1 epitope. Evidence for limited cross-reactivity between the G1 antigen of a novel hantavirus of the cotton rat and that of FCV is presented.

Genetic and phylogenetic analyses of hantaviral sequences amplified from archival tissues of deer mice (Peromyscus maniculatus nubiterrae) captured in the eastern United States

“…Recent comparisons of S and M segment sequences of PUU virus amplified from tissues of bank voles (Clethrionomys 91areolus) trapped in Udmurtia and P U U virus isolates from Bashkiria and Sotkamo indicate that the degree of sequence similarity between P U U virus strains is dependent on geographic origin [27]. Similarly, sequence analyses of HTN and FC viruses indicate geographic dependence [13,26,35,36].…”

“…In this highly conserved immunodominant domain, defined by amino acids 59 to 89 [13], Monongahela virus strains differed by 3 residues (Fig. lb) from NY virus and from multiple strains of FC virus from throughout the western United States and Canada [13,16]. In a ll40-nt region of the G2-encoding M segment, Monongahela differed from FC and NY viruses by 2.6% and 2.9%, respectively, at the amino acid level, despite the 81.1% to 82.8% nucleotide sequence similarity.…”

“…In this highly conserved immunodominant domain, defined by amino acids 59 to 89 [13], Monongahela virus strains differed by 3 residues (Fig. lb) from NY virus and from multiple strains of FC virus from throughout the western United States and Canada [13,16].…”

Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus

“…Each hantavirus species is associated with a single principal rodent host species (8), suggesting that hantaviruses and rodents share a lengthy coevolutionary history. Deer mice (Peromyscus maniculatus) are the principal reservoir hosts for SNV, which causes the great majority of HCPS cases in North America (9)(10)(11). Morphologic examination of the cells that express viral antigen in the tissues of infected deer mice reveals that they, as with infected human cells, are of endothelial origin (12).…”

Experimental infection model for Sin Nombre hantavirus in the deer mouse ( Peromyscus maniculatus )

“…HFRS occurs in Asia and Europe, with a case fatality ratio of 0.1% to 10%. HCPS was first recognized after a 1993 outbreak in the Four Corners region of the southwestern United States (1)(2)(3). HCPS occurs only in North and South America (4).…”