A Case Study of Two Rodent-Borne Viruses: Not Always the Same Old Suspects

Abstract

Two Old World rodents, house mice (Mus musculus) and Norway rats (Rattus norvegicus), were introduced into and established populations on every continent, save Antarctica. With their travels, they concomitantly introduced several zoonotic agents capable of causing human diseases. Two viruses-Lymphocytic choriomeningitis virus (LCMV; genus Arenavirus with mice) and Seoul virus (SEOV; genus Hantavirus with rats)-can cause chronic infections within their respective rodent hosts, resulting in persistent or lifelong sporadic shedding of virus through secreta and excreta. Although the prevalence of infection within their wild rodent hosts can exceed 25% among mice infected with LCMV and 50% among rats infected with SEOV, acute human disease resulting from direct transmission from wild rodents is rarely reported even though both species live in close coexistence with humans. The usual "classic" zoonotic cycle of transmission from wild rodent reservoirs to humans now includes multiple unusual/unexpected routes. The largest described outbreaks of human disease caused by these viruses are linked to pet rodents. A novel reservoir host, the golden hamster, has supplanted house mice as the major source of LCMV infection, and SEOV outbreaks are linked to fancy rats kept as pets. Following LCMV, and to a lesser extent SEOV, outbreaks or infections associated with lab animals and/or cultured tissues derived from mice and hamsters have led to hundreds of cases of LCMV among laboratory workers, and SEOV has been detected among cell-cultured tissues. Additionally, LCMV is now a recognized source of severe congenital disease and is the unexpected source of severe and often fatal disease among solid organ recipients. Although the extensive usual and unusual routes of LCMV infection are exceptional there are many parallels with SEOV emergence.

Wild Rats, Laboratory Rats, Pet Rats: Global Seoul Hantavirus Disease Revisited

“…In the Far East, and particularly in China, extensive annual mixed epidemics, caused by prototype Hantaan orthohantavirus (HTNV) and/or SEOV, resulted in tens of thousands of human infections yearly. In contrast, although American authors once called “ the SEOV prevalence in [wild] rats in many United States cities among the highest recorded globally ” [11,12,13], there has been little noticeable impact over the subsequent three decades on human morbidity and/or mortality in North America. Similarly, North-American pet rats have had only limited reported consequences for public health so far [2].…”

“…Similarly, North-American pet rats have had only limited reported consequences for public health so far [2]. The novel notion, however, that even fancy pet rats might infect their owners or breeders with a zoonotic agent (SEOV), previously thought to be limited to wild rats, has the potential to dramatically change our insights about the global importance of rat-transmitted HFRS, since pet rat trade is international, and likely also to be found beyond Europe and North America [13].…”

“…Additionally, outbreaks among laboratory workers in Asia, Russia, and Europe in the 1960s and 1970s, associated with SEOV-infected laboratory rats [13], played a pivotal role in understanding the “new” human illness, later called HFRS after a World Health Organization (WHO) meeting, during which the clinical characteristics of HFRS were, be it succinctly, described [14]. This early clinical and epidemiological knowledge was overshadowed a decade later with the discovery of a new and often lethal disease caused by SNV or ANDV, and called HCPS [15].…”

“…This was in spite of SEOV-infected wild brown rats being continuously found throughout Japan [66,67]. This situation was virtually the same worldwide for over three decades, until the recent rediscovery of SEOV-HFRS in the West since 2012 [13]. This observation underlines the diagnostic difficulties in detecting mild and “atypical” HFRS clinical disease in the Far East and probably worldwide, including on the African continent [1,7,68].…”

“…The remarkably similar symptomatology of these three AKI cases, all rapidly transient, led Belgian nephrologists to report the first (but still surprisingly valid) Western purely clinical description of SEOV-nephropathy in 1979 [93], i.e., three years before the publication of the causative pathogen itself [8]. This new scenario of HFRS originating from exposure to infected laboratory rats was recently called a “second twist of SEOV exposure” involving unusual interactions with rats, outside the realm of exposure to wild R. norvegicus, with a “third twist” being the exposure to SEOV-infected pet rats [13].…”