Genetic diversity, distribution, and serological features of hantavirus infection in five countries in South America

Abstract

Since 1995 when the first case of hantavirus pulmonary syndrome (HPS) was reported in Patagonia, there have been more than 400 cases of HPS reported in five countries in South America. The first case of HPS was associated with Andes (AND) virus. In this study, we report on the genetic diversity, geographical distribution, and serological features of hantavirus infection in six countries in South America based on 87 HPS cases from Argentina, Bolivia, Chile, Paraguay, and Uruguay. An early immunoglobulin M (IgM), IgA, and IgG humoral response was observed in almost all HPS cases. The IgM response appears to peak 1 or 2 days after the onset of symptoms. Peak IgG antibody titers occur mostly after the first week. Low IgG titers or the absence of IgG was associated with higher mortality rates. The IgA response peaks around day 15 and then rapidly decreases. The results of phylogenetic analysis based on partial M-fragment G1- and G2-encoding sequences showed that HPS cases from the five countries were infected with viruses related to AND or Laguna Negra (LN) virus. Within AND virus-infected persons, at least five major genetic lineages were found; one lineage was detected in Uruguayan and Argentinean cases from both sides of the Rio de la Plata river. Two Paraguayan patients were infected with a virus different from LN virus. According to the results of phylogenetic analyses, this virus probably belongs to a distinct lineage related more closely to the AND virus than to the LN virus, suggesting that there is probably an Oligoryzomys-borne viral variant circulating in Paraguay. These studies may contribute to a better understanding of hantavirus human infection in South America.

FIG. 1

Andes virus-specific IgG, IgA, and IgM antibody responses in 147 HPS acute or recent convalescent serum samples. Assay results on sera collected from one individual at different times are shown connected by a line. Each point represents the median daily value for the data group studied. O.D., optical density.

FIG. 2

IgG responses in surviving (○) and nonsurviving (▴) patients with acute infections of AND virus. Time (in days after onset of symptoms) is shown on the x axis, and optical density (1:400) is shown on the y axis. The data for five children less than 13 years old who died and six children less than 13 years who survived are included here. The solid line represents the mean IgG values for survivors; the dotted line represents the mean IgG values for nonsurvivors (each point [●] is the average IgG value for a consecutive 2-day interval).

FIG. 3

Phylogenetic relationship of hantaviruses based on nucleotide and amino acid sequences of three M-segment PCR fragments (nt 88 to 281 and 1736 to 1987 of G1 and nt 2721 to 2946 of G2). The lengths of the lines are proportional to genetic distances. The values next to the branches indicate the bootstrapping confidence limits (as percentages) from 500 replicates. (A) Nucleotide sequences were analyzed by the MP method (DNAPARS) using the PHYLIP package. Viral sequences geographically related to representative cases for each lineage are shown within the dotted lines. (B) Putative amino acid sequences were analyzed by the MP method (PROTPARS) using the PHYLIP package. The map shows the geographic distribution of the different virus lineages related to HPS cases. Sequences shown in roman type (not bold) were obtained from GeneBank.

FIG. 4

Sequence comparisons of the different Andes lineages and American HPS hantaviruses. The frequency (F) versus the percentage of similarity (S) from a total of 76 samples obtained after comparison of 5,700 paired sequences of a 226-nt G2 fragment (nt 2721 to 2946). Striped bars represent different sequences belonging to the same AND lineage. White bars represent sequences belonging to different AND lineages or viruses from the six countries in South America studied. Black bars represent North American HPS viruses, American viruses, or viruses from different hemispheres. The AND lineages include 14 AND Nort samples, 16 AND Cent Bs.As. samples, 5 AND Cent Plata sequences, 3 AND Cent Lec sequences, and 29 AND Sout sequences. North American HPS viruses include SN, NY, BCC, and BAY. South American HPS viruses include LN, Parag3/98, Parag1/98, and Arg-Bol/98. MACIEL virus was also included in the analysis.