Presence of Segmented Flavivirus Infections in North America - Volume 26, Number 8—August 2020 - Emerging Infectious Diseases journal - CDC

Presence of Segmented Flavivirus Infections in North America - Volume 26, Number 8—August 2020 - Emerging Infectious Diseases journal - CDC

Volume 26, Number 8—August 2020

Research

Presence of Segmented Flavivirus Infections in North America

Kurt J. Vandegrift1, Arvind Kumar1, Himanshu Sharma, Satyapramod Murthy, Laura D. Kramer, Richard Ostfeld, Peter J. Hudson, and Amit Kapoor 

Author affiliations: Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, Pennsylvania, USA (K.J. Vandegrift, P.J. Hudson); Center for Vaccines and Immunity, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA (A. Kumar, H. Sharma, S. Murthy, A. Kapoor); Wadsworth Center, New York State Department of Health, Albany, New York, USA (L.D. Kramer); University of Albany-SUNY School of Public Health, Albany (L.D. Kramer); The Cary Institute for Ecosystem Science, Millbrook, New York, USA (R. Ostfeld); Ohio State University College of Medicine and Public Health, Columbus (A. Kapoor)

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Abstract

Identifying viruses in synanthropic animals is necessary for understanding the origin of many viruses that can infect human hosts and developing strategies to prevent new zoonotic infections. The white-footed mouse, Peromyscus leucopus, is one of the most abundant rodent species in the northeastern United States. We characterized the serum virome of 978 free-ranging P. leucopus mice caught in Pennsylvania. We identified many new viruses belonging to 26 different virus families. Among these viruses was a highly divergent segmented flavivirus whose genetic relatives were recently identified in ticks, mosquitoes, and vertebrates, including febrile humans. This novel flavi-like segmented virus was found in rodents and shares ˂70% aa identity with known viruses in the highly conserved region of the viral polymerase. Our data will enable researchers to develop molecular reagents to further characterize this virus and its relatives infecting other hosts and to curtail their spread, if necessary.

Most human infectious diseases have a zoonotic origin (1). RNA viruses are remarkable in their ability to evolve and infect a wide range of hosts, primarily due to their error-prone replication, small genome size, and ability to adapt (2). Recent studies describing human infections with animal coronaviruses and paramyxoviruses illustrate well the high zoonotic potential of animal RNA viruses (3). Not all viruses at the human–animal interface can breach the species barrier, and successful cross-species transmission often requires repeated introduction coupled with favorable circumstances (3). These multiple exposures provide increased opportunity for viral adaptation, and because humans are frequently exposed to viruses from synanthropic hosts, this channel becomes a likely route of infection. As such, we need to identify and characterize viruses from synanthropic animals to understand the origins of many human viruses and obtain insights into the emergence of potential zoonotic infections (1).

Rodents and bats are common sources of potential zoonotic viruses (4). In the northeastern United States, the white-footed mouse (Peromyscus leucopus) is one of the most widespread and abundant rodent species. These mice are highly adaptable, commonly become synanthropic, and invade human domiciles. Humans are exposed to a wide range of viruses from these mice, either directly as is the case with hantaviruses or indirectly through vectors such as ticks. These rodents are also known to harbor a range of zoonotic pathogens, including the tickborne Borrelia burgdorferi, which causes Lyme disease, and Anaplasma phagocytilium, which causes anaplasmosis (5). White-footed mice can also act as reservoirs for bacteria that are causative agents of Rocky Mountain spotted fever, tularemia, plague, and bartonellosis and for protozoans responsible for babesiosis, giardiasis, toxoplasmosis, and cryptosporidiosis (6). Infectious viruses reported in P. leucopus include lymphocytic choriomeningitis virus, Powassan or deer tick encephalitis virus, and hantaviruses (7,8).

The genome of flaviviruses is composed of a single-stranded positive-sense RNA that codes for a single polyprotein. The genome of Jingmen tick virus (JMTV), which was first identified in 2014 from ticks in the Jingmen province of China (9), is composed of 4 single-stranded positive-sense RNA segments, 2 of which encode a polymerase protein (NS5) and a helicase protein (NS3) that show close phylogenetic relatedness with the corresponding proteins of classical flaviviruses (9). Later, several genetically diverse relatives of JMTV were found in several species of ticks, insects, and mammals (9–13). Together, these JMTV-like viruses are highly diverse and show differences in the number of genomic segments as well as protein coding strategies (9,10,12). In 2018, a metagenomics study revealed the presence of JMTV-like sequences in serum samples from human patients with Crimean-Congo hemorrhagic fever in Kosovo (14). Two studies published in 2019 reported the presence of JMTV sequences in humans in China with febrile illness and a history of recent tick bites (15,16). To date, no information is available on the presence of JMTV infections in insects, ticks, or vertebrates in North America.

Knowledge about viruses infecting P. leucopus and the levels to which humans are being exposed is limited. Although several studies have examined the prevalence of hantaviruses (17) and highly diverse hepaciviruses (18), there has been no attempt to characterize the blood virome of these common rodents. We used an unbiased, metaviromics approach to identify all viruses in the serum samples of 978 free-ranging white-footed mice captured over a period of 7 years from suburban and wild areas of Pennsylvania.