ABSTRACT
The Ghana virus (GhV) is phylogenetically related to the zoonotic henipaviruses Nipah (NiV) and Hendra virus. Although GhV uses the highly conserved receptor ephrin-B2, the fusogenicity is restricted to cell lines of bat origin. Furthermore, the surface expression of the GhV attachment glycoprotein (G) is reduced compared to NiV and most of this protein is retained in the endoplasmic reticulum (ER). Here, we generated truncated as well as chimeric GhV G proteins and investigated the influence of the structural domains (cytoplasmic tail, transmembrane domain, ectodomain) of this protein on the intracellular transport and the fusogenicity following coexpression with the GhV fusion protein (F). We demonstrate that neither the cytoplasmic tail nor the transmembrane domain is responsible for the intracellular retention of GhV G. Furthermore, the cytoplasmic tail of GhV G modulates the fusogenicity of GhV F and therefore controls the species-restricted fusogenicity of the GhV surface glycoproteins.
Subject(s)
Cell Fusion , Henipavirus/metabolism , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/metabolism , Viral Fusion Proteins/metabolism , Animals , Cell Line , Chiroptera , Chlorocebus aethiops , HEK293 Cells , Henipavirus/genetics , Host Specificity , Humans , Protein Domains , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sequence Deletion , Vero Cells , Viral Envelope Proteins/genetics , Viral Fusion Proteins/geneticsABSTRACT
Bats harbor a plethora of viruses with an unknown zoonotic potential. In-depth functional characterization of such viruses is often hampered by a lack of virus isolates. The genome of a virus closely related to human mumps viruses (hMuV) was detected in African fruit bats, batMuV. Efforts to characterize batMuV were based on directed expression of the batMuV glycoproteins or use of recombinant chimeric hMuVs harboring batMuV glycoprotein. Although these studies provided initial insights into the functionality of batMuV glycoproteins, the host range, replication competence, immunomodulatory functions, virulence, and zoonotic potential of batMuV remained elusive. Here, we report the successful rescue of recombinant batMuV. BatMuV infects human cells, is largely resistant to the host interferon response, blocks interferon induction and TNF-α activation, and is neurotoxic in rats. Anti-hMuV antibodies efficiently neutralize batMuV. The striking similarities between hMuV and batMuV point at the putative zoonotic potential of batMuV.
Subject(s)
Chiroptera/virology , Immune Evasion/immunology , Mumps virus/immunology , Mumps/virology , Neurotoxicity Syndromes/etiology , Virus Internalization , Virus Replication , Animals , Female , Humans , Mumps virus/pathogenicity , Neurotoxicity Syndromes/pathology , Rats , Rats, Inbred LewABSTRACT
BACKGROUND: Avalanche transceivers are essentials tools in locating persons who were buried by an avalanche. In the past few years, avalanche transceivers have become widely available and affordable, but it is largely unknown whether they are a source of electromagnetic interference for implanted cardiac devices. We aimed to determine the potential interaction between avalanche transceivers and pacemakers or implantable cardioverter defibrillators (ICDs). METHODS: One hundred and one patients, 41 with pacemakers and 60 with ICDs, were enrolled (mean age 66 ± 15 years). Four avalanche transceivers (Pieps DSP [Pieps GmbH, Lebring, Austria], Ortovox x1, Ortovox m2, and Ortovox f1 [Otovox Sportartikel GmbH, Taufkirchen, Germany]) were evaluated in transmit as well as in receive mode. Surface electrocardiograms, intracardiac electrograms, and marker channels were continuously recorded and observed by an experienced physician. Electromagnetic interference events were categorized as direct interference with the function of the implanted device itself or as interference with the telemetric communication without compromising device function. RESULTS: Among all patients, there was no interference with the intrinsic function of their pacemakers or ICDs. A total of 120 episodes of telemetry interference occurred in 48% of the patients. Of those episodes, 112 of 404 (28%) were observed in transmit and eight of 404 (2%) in receive mode (P < 0.0001). The digital avalanche transceiver (Pieps DSP) was associated with significantly less telemetry interference (20/202; 10%) than the analog transceiver (Ortovox f1) (39/202; 19%) (P = 0.0108). CONCLUSIONS: Avalanche transceivers are safe for patients with pacemakers and ICDs. Despite the observed telemetry interferences, the intrinsic function of the implanted devices was never compromised.
