Genetic investigation of novel hantaviruses causing fatal HPS in Brazil

Abstract

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.

Circulation of hantaviruses in the influence area of the Cuiabá-Santarém Highway

“…Since 1995, when the first HPS case was identified in Castelo dos Sonhos, PA (Johnson et al 1999), an increasing number of cases have been registered in 12 municipalities located near or around this Highway, in the three states under its influence area. MT ranks fourth in the amount of HPS cases reported in Brazil and first in the Pan Amazon area, with over 168 cases registered between 1999-December of 2009, in about 24 municipalities.…”

“…In Brazil, since the first cases of HPS were reported in Juquitiba (in 1993), state of São Paulo (SP), Southeastern Brazil (Iversson et al 1994) and Castelo dos Sonhos, a district of Altamira municipality, state of Pará (PA), Northern Brazil (in 1995) (Johnson et al 1999), approximately 1,209 cases of HPS were reported as of December 31, 2008. Of these, 20.7% (n = 232) occurred in the Brazilian Amazon region, mainly in the states of Mato Grosso (MT) and PA; however, the states of Amazonas (AM), Rondônia (RO) and Maranhão (MA) have also reported HPS cases.…”

Serosurvey of hantavirus infection in humans in the border region between Brazil and Argentina

“…We suggest Araraquara and Juquitiba as possible viruses circulating in this study area, based on the geographical distribution of these viruses and the assumption that no other strain is in circulation. However, the possibility of an unknown hantavirus or one not yet reported in Brazil 31,32 , or even a hantavirus previously reported in Argentina, given the proximity of this region with the neighboring country, cannot be discarded.…”

Andes virus associated with hantavirus pulmonary syndrome in northern Argentina and determination of the precise site of infection.

“…The major symptoms of this syndrome are fever, myalgia, headache, and gastrointestinal and cardiopulmonary dysfunction with a high case fatality rate. 4,5 An increasing number of hantaviruses associated with human disease have been identified not only in North America, but also in South America (Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay, [6][7][8] ) and recently in Central America (Panama. 9 ) Person-to-person transmission was first documented during an outbreak of HPS in southern Argentina in 1996, [10][11][12] and most likely in two family clusters in Chile in 1997, 13 all associated with Andes (AND) virus.…”