Confirmation of Choclo virus as the cause of hantavirus cardiopulmonary syndrome and high serum antibody prevalence in Panama

Abstract

Choclo virus (CHOV) was described in sigmodontine rodents, Oligoryzomys fulvescens, and humans during an outbreak of hantavirus cardiopulmonary syndrome (HCPS) in 1999-2000 in western Panama. Although HCPS is rare, hantavirus-specific serum antibody prevalence among the general population is high suggesting that CHOV may cause many mild or asymptomatic infections. The goals of this study were to confirm the role of CHOV in HCPS and in the frequently detected serum antibody and to establish the phylogenetic relationship with other New World hantaviruses. CHOV was cultured to facilitate the sequencing of the small (S) and medium (M) segments and to perform CHOV-specific serum neutralization antibody assays. Sequences of the S and M segments found a close relationship to other Oligoryzomys-borne hantaviruses in the Americas, highly conserved terminal nucleotides, and no evidence for recombination events. The maximum likelihood and maximum parsimony analyses of complete M segment nucleotide sequences indicate a close relationship to Maporal and Laguna Negra viruses, found at the base of the South American clade. In a focus neutralization assay acute and convalescent sera from six Panamanian HCPS patients neutralized CHOV in dilutions from 1:200 to 1:6,400. In a sample of antibody-positive adults without a history of HCPS, 9 of 10 sera neutralized CHOV in dilutions ranging from 1:100 to 1:6,400. Although cross-neutralization with other sympatric hantaviruses not yet associated with human disease is possible, CHOV appears to be the causal agent for most of the mild or asymptomatic hantavirus infections, as well as HCPS, in Panama.

Figure 1

A. Maximum likelihood analysis of 1302 nt of the S segment of 25 hantaviruses. Tree based on the GTR + G (0.6787) + I(0.3440) model of nucleotide evolution. Numbers associated with node are Bayesian posterior probabilities. Model for Bayesian analyses is the same used for Maximum Likelihood (topologies were identical). B. Single most parsimonious tree based on 675 informative of 1302 total base pairs of the N protein. Characters were weighted based on a rescaled consistency index. Third base positions were analyzed using transversions only. Tree length = 587.794; RCI = 0.5148. Numbers above branches represent percentage of 1000 bootstrap replications supporting each node. Nodes with less than 50% support are collapsed. C. Maximum likelihood analysis of 3465 nt of the M segment of 16 hantaviruses. Tree based on the GTR + G(0.3439) model of nucleotide evolution. Numbers associated with node are Bayesian posterior probabilities. Model for Bayesian analyses is the same used for Maximum Likelihood (topologies were identical). D. Single most parsimonious tree based on 2077 informative of 3465 total base pairs of the GPC gene. Tree length = 6307; CI = 0.4635. Third base positions were analyzed using transversions only. Numbers above branches represent percentage of 1000 bootstrap replications supporting each node. Nodes with less than 50% support are collapsed.