Deciphering the Hantavirus Host Range Combining Virology and Species Distribution Models with an Emphasis on the Yellow Pygmy Rice Rat (Oligoryzomys flavescens)

Abstract

Hantaviruses are the causative agents of hantavirus pulmonary syndrome (HPS) in the Americas. In Central and South America, 28 hantavirus lineages were associated with different Sigmodontinae rodents. Of these, Lechiguanas hantavirus was initially described as a lineage associated with HPS cases in the central region of Argentina. Initial studies on the rodent hosts and viral lineages performed between 1999 and 2005 showed that HPS cases in Uruguay were distributed mostly in the southern region of the country, and that the Lechiguanas hantavirus (LECV) and the closely related Andes Central Plata hantaviruses were the viral lineages most frequently associated with HPS cases, both carried by the yellow pygmy rice rat (Oligoryzomys flavescens). Although these rodents are present all across the Uruguayan territory, determining the extent of the risk areas for hantavirus transmission based on the distribution of the infected rodents may be a useful tool for disease control and prevention. Distribution models are positioned as an effective instrument in the prediction of diseases affecting human health. Assessment of the potential distribution of rodent reservoir hosts and analysis of the influence of environmental factors on hantavirus transmission can help to understand the spatial patterns of disease transmission risk. In the present study, virological studies and species distribution models were integrated to understand the hantavirus infection risk pattern in Uruguay. Virological analyses confirmed that in Uruguay, the primary hantavirus reservoir host for both viral lineages is the yellow pygmy rice rat. Additionally, we report an Azara's grass mouse (Akodon azarae) infected with the Andes Central Plata viral lineage. Based on the seropositive and nonseropositive yellow pygmy rice rats tested, the distribution models emphasized that favorable environmental conditions for the infected rodents are mainly related to the availability of human-disturbed rural environments with high humidity. We conclude that the innovative application of the methodologies reported herein allowed for the assessment of the current risk territory for HPS in Uruguay.

Figure 1

(a) Uruguay as a study area in the general context of South America. (b) Distribution of serological analysis points for Oligoryzomys flavescens rodents in Uruguay. Territories sampled for rodents between 2012 and 2014 are shown with black dots, and territories sampled before 2012 are shown with gray dots. The country layer was obtained from https://www.naturalearthdata.com and licensed CC BY. The maps were developed using QGIS (https://www.qgis.org) with the composer tool. The final composition was created using CorelDRAW 2018.

Figure 2

(a) Grids used to train the spatial model; grids sampled with hantavirus seronegative are indicated in gray, and grids with hantavirus seropositive (or hantavirus reservoir zone) in red. (b) Results of the spatial favorability model for O. flavescens as a hantavirus reservoir host, showing the area unfavorable or unreachable for the rodent as a hantavirus host (with spatial favorability values or F < 0.2) in pink and the reachable area (with spatial favorability values or F ≥ 0.2) in red. (c) Results of the environmental favorability model for O. flavescens as a hantavirus reservoir, showing the most favorable areas for the presence of a hantavirus reservoir or seropositive rodents (favorability values or F ≥ 0.8) in red, the intermediately favorable areas (0.2 ≤ F < 0.8) in pink, and the unfavorable areas (F < 0.2) in gray. The country layer was obtained from https://www.naturalearthdata.com and licensed CC BY. The grid layer was created with the tool “create grid” of the software QGIS https://www.qgis.org.

Figure 3

Maximum likelihood phylogenetic analysis: phylogeny was deduced using previously reported hantavirus and Uruguayan partial S segment sequences (rodents and HPS cases). The sequences reported here are colored in purple, and capture sites are indicated (GenBank accession numbers: ON544080, ON544081, ON544082, ON544083, and ON544084). Hantaan (AB127988) and Seoul (NC005236) sequences were used as the outgroup species. Approximate likelihood-ratio test (aLRT) was used to assess the statistical support of the clades, with only significant values shown. Abbreviations of hantavirus species and lineages: HTNV = Hantaan, SEOV = Seoul, BAYV = Bayou, CATV = Catacamas, MULV = Muleshoe, OROV = Rio de Oro, LSCV = Limestone Canyon, MTNV = Montano, RIOSV = Rio Segundo, ELMCV = El Moro Canyon, CARV = Carrizal, HUIV = Huitzilac, CADV = Caño Delgadito, SNV = Sin Nombre, JUQV = Juquitiba, ITAPV = Itapúa, ARAUV = Araucaria, PGMV = Pergamino, MACV = Maciel, ARAV = Araraquara, PARV = Paranoa, ANDV = Andes, CASV = Castelo Dos Sonhos, TUNV = Tunari, BMJV = Bermejo, NEEMV = Neembucú, LECV = Lechiguanas, CHOV = Choclo, JABV = Jaborá, LNV = Laguna Negra, ALPV = Alto Paraguay, RIOMV = Río Mamoré, and MARV = Maripa.