Truncated Hantavirus Nucleocapsid Proteins for Serotyping Sin Nombre, Andes, and Laguna Negra Hantavirus Infections in Humans and Rodents

Abstract

Sin Nombre virus (SNV), Andes virus (ANDV), and Laguna Negra virus (LANV) have been known as the dominant causative agents of hantavirus pulmonary syndrome (HPS). ANDV and LANV, with different patterns of pathogenicity, exist in a sympatric relationship. Moreover, there is documented evidence of person-to-person transmission of ANDV. Therefore, it is important in clinical medicine and epidemiology to know the serotype of a hantavirus causing infection. Truncated SNV, ANDV, and LANV recombinant nucleocapsid proteins (trNs) missing 99 N-terminal amino acids (trN100) were expressed using a baculovirus system, and their applicability for serotyping SNV, ANDV, and LANV infection by the use of enzyme-linked immunosorbent assays (ELISA) was examined. HPS patient sera and natural-reservoir rodent sera infected with SNV, ANDV, and LANV showed the highest optical density (OD) values for homologous trN100 antigens. Since even patient sera with lower IgM and IgG antibody titers were serotyped, the trN100s are therefore considered useful for serotyping with early-acute-phase sera. In contrast, assays testing whole recombinant nucleocapsid protein antigens of SNV, ANDV, and LANV expressed in Escherichia coli detected homologous and heterologous antibodies equally. These results indicated that a screening ELISA using an E. coli-expressed antigen followed by a serotyping ELISA using trN100s is useful for epidemiological surveillance in regions where two or more hantavirus species cocirculate.

Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the Mechanism for Ribonucleoprotein Complex Formation

“…Hantavirus NP is the major antigen that elicits early serological responses in infected humans and has been used as a biomarker to develop antibodies for epidemiological surveillance in regions where various hantavirus species cocirculate (4,39). NP has also been shown to elicit protection against hantavirus infection in animals and therefore was considered for use as a component of a vaccine (40,41).…”

Development of a serotyping enzyme-linked immunosorbent assay system based on recombinant truncated hantavirus nucleocapsid proteins for New World hantavirus infection

“…Enzyme-linked immunosorbent assay (ELISA) using trNP50 differentiated successfully infections with four different serotypes of Old World hantavirus: Hantaan, Seoul, Dobrava, and Thailand viruses in HFRS patient and rodent sera (Araki et al, 2001;Nakamura et al, 2008). ELISA using trNP lacking 99 aa of the N-terminal end of the NP (trNP100) differentiated successfully infections with three different serotypes of New World hantaviruses: Sin Nombre virus (SNV), Andes virus (ANDV) and Laguna Negra virus (LANV) in HPS patient and rodent sera (Koma et al, 2010). Therefore, the serotyping ELISA using trNPs is a more rapid, safe and simple method as a substitute for the neutralization test, which has been the only serological assay for determining the serotype (Araki et al, 2001;Koma et al, 2010;Nakamura et al, 2008).…”

Laguna Negra Virus Infection Causes Hantavirus Pulmonary Syndrome in Turkish Hamsters (Mesocricetus brandti)

“…Of the South American hantaviruses, ANDV case fatality rates are approximately 40%, 1 whereas LNV has a lower fatality rate of approximately 15%. [8][9][10] HPS caused by hantavirus infection in humans is primarily characterized by an influenza-like prodrome with rapidly progressive respiratory disease, pulmonary edema, cardiogenic depression, and shock. 7,8,26,27 Hallmark pathologic features of HPS include interstitial pneumonia, edema, and perivasculitis in the lungs and generalized infection of endothelial cells.…”