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.

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.

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.