Abstract
Long-tailed pygmy rice rats (Oligoryzomys longicaudatus) are principal reservoir hosts of Andes virus (ANDV) (Bunyaviridae), which causes most hantavirus cardiopulmonary syndrome cases in the Americas. To develop tools for the study of the ANDV-host interactions, we used RNA-Seq to generate a de novo transcriptome assembly. Splenic RNA from five rice rats captured in Chile, three of which were ANDV-infected, was used to generate an assembly of 66,173 annotated transcripts, including noncoding RNAs. Phylogenetic analysis of selected predicted proteins showed similarities to those of the North American deer mouse (Peromyscus maniculatus), the principal reservoir of Sin Nombre virus (SNV). One of the infected rice rats had about 50-fold more viral burden than the others, suggesting acute infection, whereas the remaining two had levels consistent with persistence. Differential expression analysis revealed distinct signatures among the infected rodents. The differences could be due to 1) variations in viral load, 2) dimorphic or reproductive differences in splenic homing of immune cells, or 3) factors of unknown etiology. In the two persistently infected rice rats, suppression of the JAK-STAT pathway at Stat5b and Ccnot1, elevation of Casp1, RIG-I pathway factors Ppp1cc and Mff, and increased FC receptor-like transcripts occurred. Caspase-1 and Stat5b activation pathways have been shown to stimulate T helper follicular cell (TFH) development in other species. These data are also consistent with reports suggestive of TFH stimulation in deer mice experimentally infected with hantaviruses. In the remaining acutely infected rice rat, the apoptotic pathway marker Cox6a1 was elevated, and putative anti-viral factors Abcb1a, Fam46c, Spp1, Rxra, Rxrb, Trmp2 and Trim58 were modulated. Transcripts for preproenkephalin (Prenk) were reduced, which may be predictive of an increased T cell activation threshold. Taken together, this transcriptome dataset will permit rigorous examination of rice rat-ANDV interactions and may lead to better understanding of virus ecology.
Highlights
Several species of hantaviruses have been identified as human pathogens, and some cause hantavirus cardiopulmonary syndrome (HCPS), a disease that has killed hundreds in South America [3,4]
Rice rats #18 (RR18), RR29, RR31 were seropositive for hantavirus nucleocapsid as determined by ELISA [18]
The infection status for all three seropositive animals was confirmed by qRT-PCR of S segment genome equivalents (GE) (Fig 1A), indicating greater sensitivity of PCR relative to RNA-seq
Summary
Several species of hantaviruses (family Bunyaviridae) have been identified as human pathogens (reviewed in [1,2]), and some cause hantavirus cardiopulmonary syndrome (HCPS), a disease that has killed hundreds in South America [3,4]. The long-tailed pygmy rice rat (Oligoryzomys longicaudatus, “rice rat”) is found throughout most of southern South America and is the principal reservoir of Andes virus (ANDV) [5]. Pathogenic hantaviruses circulate in rodent reservoirs without causing substantial disease, and the reservoirs are thought to remain infected with hantavirus for life (reviewed in [2]), despite the production of neutralizing antibodies [6]. Despite the importance of the rice rat as a reservoir host for important human pathogens, little is known about its host response during infections
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