Characterization of human antibody responses to four corners hantavirus infections among patients with hantavirus pulmonary syndrome

Abstract

Hantavirus pulmonary syndrome (HPS) is a human disease caused by a newly identified hantavirus, which we will refer to as Four Corners virus (FCV). FCV is related most closely to Puumala virus (PUU) and to Prospect Hill virus (PHV). Twenty-five acute HPS serum samples were tested for immunoglobulin G (IgG) and IgM antibody reactivities to FCV-encoded recombinant proteins in Western blot (immunoblot) assays. All HPS serum samples contained both IgG and IgM antibodies to the FCV nucleocapsid (N) protein. FCV N antibodies cross-reacted with PUU N and PHV N proteins. A dominant FCV N epitope was mapped to the segment between amino acids 17 and 59 (QLVTARQKLKDAERAVELDPDDVNKSTLQSRRAAVSALETKLG). All HPS serum samples contained IgG antibodies to the FCV glycoprotein-1 (Gl) protein, and 21 of 25 serum samples contained FCV Gl IgM antibodies. The FCV Gl antibodies did not cross-react with PUU Gl and PHV Gl proteins. The FCV GI type-specific antibody reactivity mapped to a segment between amino acids 59 and 89 (LKIESSCNFDLHVPATTTQKYNQVDlWTKKSS). One hundred twenty-eight control serum samples were tested for IgG reactivities to the FCV N and Gl proteins. Nine (7.0%) contained FCV N reactivities, 3 (2.3%) contained FCV Gl reactivities, and one (0.8%) contained both FCV N and FCV GI reactivities. The epitopes recognized by antibodies present in control serum samples were different from the epitopes recognized by HPS antibodies, suggesting that the control antibody reactivities were unrelated to FCV infections. These reagents constitute a type-specific assay for FCV antibodies.

Human immune response to Puumala virus glycoproteins and nucleocapsid protein expressed in mammalian cells

“…IgG antibodies against N develop early after onset of symptoms and persist in serum for years, whereas a slower IgG response against the glycoproteins has been described earlier using EIA [Lundkvist et al, 1993;Vapalahti et al, 1995]. In other studies, the G1-antibody responses have been shown to become detectable in the acute phase of hantavirus pulmonary syndrome, but not of PUUV or Hantaan virus infections when recombinant G1 antigens expressed in bacterial or yeast systems were used [Jenison et al, 1994;Hjelle et al, 1997]. In some reports, an early antibody response to PUUV-G1 has been shown, G2 antibodies appearing later according to inhibition EIA or slot-blot assay/ EIA [Go Ètt et al, 1997].…”

Recent Advances in Hantavirus Molecular Biology and Disease

“…High titers of IgM and IgG antibodies against hantavirus N and Gn proteins are detectable in the sera of patients during the acute phase, enabling reliable serological confirmation of infection (Bostik et al, 2000;Elgh et al, 1997;Groen et al, 1994). SNV Gn antibodies are highly specific and do not cross-react with Gn antigens of other hantaviruses Jenison et al, 1994). The most widely used serological tests for diagnosis of HCPS are IgM capture and IgG indirect ELISAs (Li et al, 2002).…”

Locations of herpes simplex virus type 2 glycoprotein B epitopes recognized by human serum immunoglobulin G antibodies

“…The deletion-mapping technique defines a segment of gB-2 that contains one or more linear antibody-binding sites but does not define the minimum epitope recognized by those antibodies. This strategy has been used extensively by our group to localize human antibodyreactive segments of the Four Corners hantavirus and human papillomavirus antigens (29)(30)(31)(32)59).…”