Genetic diversity and evolution of Hantaan virus in China and its neighbors

Author summary Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome are endemic zoonotic infectious diseases caused by hantaviruses, which have threatened public health worldwide for decades. However, our knowledge about the emergence and evolution of HTNV still need to be improved. To get more information about HTNV genetic diversity and phylogenetic features with a holistic perspective, we investigated the genetic diversity and spatial distribution of HTNV using all available whole-genome sequences of small (S) and medium (M) segments collected from 18 different regions and using a larger timescale; 11 phylogenetic groups were defined. The sequences showed geographic clustering, and divergence with recombinant or reassortment events occurred. Using the Bayesian stochastic search variable selection method, geographic origins and migration patterns of HTNV epidemics were deduced. Our data provided important biological information to better understand hantavirus evolution, transmission, and epidemics. Background Hantaan virus (HTNV; family Hantaviridae, order Bunyavirales) causes hemorrhagic fever with renal syndrome (HFRS), which has raised serious concerns in Eurasia, especially in China, Russia, and South Korea. Previous studies reported genetic diversity and phylogenetic features of HTNV in different parts of China, but the analyses from the holistic perspective are rare. Methodology and principal findings To better understand HTNV genetic diversity and gene evolution, we analyzed all available complete sequences derived from the small (S) and medium (M) segments with bioinformatic tools. Eleven phylogenetic groups were defined and showed geographic clustering; 42 significant amino acid variant sites were found, and 19 of them were located in immune epitopes; nine recombinant events and eight reassortments with highly divergent sequences were found and analyzed. We found that sequences from Guizhou showed high genetic divergence, contributing to multiple lineages of the phylogenetic tree and also to the recombination and reassortment events. Bayesian stochastic search variable selection analysis revealed that Heilongjiang, Shaanxi, and Guizhou played important roles in HTNV evolution and migration; the virus may originate from Zhejiang Province in the eastern part of China; and the virus population size expanded from the 1980s to 1990s. Conclusions/significance These findings revealed the original and evolutionary features of HTNV, which will help to illustrate hantavirus epidemic trends, thus aiding in disease control and prevention.