Tick-Borne Transmission of Murine Gammaherpesvirus 68.

Valeria Hajnická,Zuzana Halásová,Petra Belvončíková,Iveta Štibrániová,Mirko Slovák,Patricia A Nuttall,Viera Holíková,Pavlína Bartíková,Michaela Vrbová,Rosemary S Hails,Peter Pančík,Marcela Kúdelová

doi:10.3389/fcimb.2017.00458

Abstract

Herpesviruses are a large group of DNA viruses infecting mainly vertebrates. Murine gammaherpesvirus 68 (MHV68) is often used as a model in studies of the pathogenesis of clinically important human gammaherpesviruses such as Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. This rodent virus appears to be geographically widespread; however, its natural transmission cycle is unknown. Following detection of MHV68 in field-collected ticks, including isolation of the virus from tick salivary glands and ovaries, we investigated whether MHV68 is a tick-borne virus. Uninfected Ixodes ricinus ticks were shown to acquire the virus by feeding on experimentally infected laboratory mice. The virus survived tick molting, and the molted ticks transmitted the virus to uninfected laboratory mice on which they subsequently fed. MHV68 was isolated from the tick salivary glands, consistent with transmission via tick saliva. The virus survived in ticks without loss of infectivity for at least 120 days, and subsequently was transmitted vertically from one tick generation to the next, surviving more than 500 days. Furthermore, the F1 generation (derived from F0 infected females) transmitted MHV68 to uninfected mice on which they fed, with MHV68 M3 gene transcripts detected in blood, lung, and spleen tissue of mice on which F1 nymphs and F1 adults engorged. These experimental data fulfill the transmission criteria that define an arthropod-borne virus (arbovirus), the largest biological group of viruses. Currently, African swine fever virus (ASFV) is the only DNA virus recognized as an arbovirus. Like ASFV, MHV68 showed evidence of pathogenesis in ticks. Previous studies have reported MHV68 in free-living ticks and in mammals commonly infested with I. ricinus, and neutralizing antibodies to MHV68 have been detected in large mammals (e.g., deer) including humans. Further studies are needed to determine if these reports are the result of tick-borne transmission of MHV68 in nature, and whether humans are at risk of infection.

Highlights

All vertebrates are probably infected with at least one herpesvirus species, herpesviruses are believed not to infect arthropods, and vector-mediated transmission of herpesviruses is unreported hitherto (King et al, 2011)
To test whether Murine gammaherpesvirus 68 (MHV68) can survive in ticks and be transmitted during blood-feeding, unfed adult female ticks were inoculated with 0.5 μl phosphatebuffered saline (PBS) containing 1.25 × 104 PFU of MHV68 using a digital microinjector system
Five days later, when the ticks were partially engorged, a total of six female ticks were removed from three mice and their salivary glands dissected out and assayed using a nested PCR targeting MHV68 ORF50

Summary

Introduction

All vertebrates are probably infected with at least one herpesvirus species, herpesviruses are believed not to infect arthropods, and vector-mediated transmission of herpesviruses is unreported hitherto (King et al, 2011). Tick-Borne Transmission of MHV68 systemic infection following a cell-associated viremia during primary infection. The key to survival of herpesviruses is their ability to establish life-long latent infections (Roizman and Pellett, 2001; Adler et al, 2017). Members of the subfamily Gammaherpesvirinae, which includes murid herpesvirus 4 (MuHV-4, more commonly known as murine gammaherpesvirus 68, MHV68) in the genus Rhadinovirus, establish latent infections in lymphocytes or lymphoid tissue. Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) are host (human)-specific and lack a tractable in vivo infection model (Cieniewicz et al, 2016; Habison et al, 2017). The discovery of MHV68 provided what is a much studied laboratory model for investigating virus reactivation from latency as well as host mechanisms of immune control, and the genetic basis of viral fitness in different cell types and tissues (Rajcáni and Kúdelová, 2007; Sattler et al, 2016)

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