RESUMEN
Although hantavirus pulmonary syndrome (HPS) was discovered in North America in 1993, more recent investigations have shown that the disease is a much larger problem in South America, where a greater number of cases and HPS-associated viruses have now been detected. Here we describe the genetic investigation of three fatal HPS cases from Brazil, including a 1995 case in Castelo dos Sonhos (CAS) in the state of Mato Grosso and two 1996 cases in the counties of Araraquara (ARA) and Franca (FRA), in the state of São Paulo. Reverse transcription-polymerase chain reaction (RT-PCR) products representing fragments of the hantavirus N, G1, and G2 coding regions were amplified from patient acute-phase serum samples, and the nucleotide (nt) sequences (394, 259, and 139 nt, respectively) revealed high deduced amino acid sequence identity between ARA and FRA viruses (99.2%, 96.5%, and 100%, respectively). However, amino acid differences of up to 14.0% were observed when ARA and FRA virus sequences were compared with those of the geographically more distant CAS virus. Analysis of a 643-nt N coding region and a 1734-nt predominantly G2-encoding region of ARA and CAS virus genomes confirmed that these Brazilian viruses were distinct and monophyletic with previously characterized Argentinean hantaviruses, and suggested that Laguna Negra (LN) virus from Paraguay was ancestral to both the Brazilian and Argentinean viruses. The phylogenetic tree based on the N coding fragment also placed LN in a separate clade with Rio Mamore virus from Bolivia. At the amino acid level, ARA and CAS viruses appeared more closely related to the Argentinean viruses than they were to each other. Similarly, analysis of the diagnostic 139-nt G2 fragment showed that the Juquitiba virus detected in a 1993 fatal HPS case close to São Paulo city, Brazil was closer to Argentinean viruses than to ARA or CAS viruses. These data indicate that at least three different hantavirus genetic lineages are associated with Brazilian HPS cases.
Asunto(s)
Síndrome Pulmonar por Hantavirus/virología , Orthohantavirus/genética , Anticuerpos Antivirales/sangre , Brasil , ADN Viral/análisis , Resultado Fatal , Femenino , Orthohantavirus/clasificación , Orthohantavirus/aislamiento & purificación , Humanos , Masculino , Filogenia , Reacción en Cadena de la PolimerasaRESUMEN
A large outbreak of hantavirus pulmonary syndrome (HPS) recently occurred in the Chaco region of Paraguay. Using PCR approaches, partial virus genome sequences were obtained from 5 human sera, and spleens from 5 Calomys laucha rodents from the outbreak area. Genetic analysis revealed a newly discovered hantavirus, Laguna Negra (LN) virus, to be associated with the HPS outbreak and established a direct genetic link between the virus detected in the HPS cases and in the C. laucha rodents, implicating them as the primary rodent reservoir for LN virus in Paraguay. Virus isolates were obtained from two C. laucha, and represent the first successful isolation of a pathogenic South American hantavirus. Analysis of the prototype LN virus entire S and M and partial L segment nucleotide and deduced amino acid sequences showed that this virus is unique among the Sigmodontinae-borne clade of hantaviruses. Analysis of PCR fragments amplified from a serum sample from a Chilean HPS patient, who had recently traveled extensively in Bolivia (where C. laucha are known to occur), revealed an LN virus variant that was approximately 15% different at the nucleotide level and identical at the deduced amino acid level relative to the Paraguayan LN virus. These data suggest that LN virus may cause HPS in several countries in this geographic region.