Exocytosis of Varicella-Zoster Virus Virions Involves a Convergence of Endosomal and Autophagy Pathways
نویسندگان
چکیده
UNLABELLED Varicella-zoster virus (VZV) is an extremely cell-associated herpesvirus with limited egress of viral particles. The induction of autophagy in VZV-infected monolayers is easily detectable; inhibition of autophagy leads to decreased VZV glycoprotein biosynthesis and diminished viral titers. To explain how autophagic flux could exert a proviral effect on the VZV infectious cycle, we postulated that the VZV exocytosis pathway following secondary envelopment may converge with the autophagy pathway. This hypothesis depended on known similarities between VZV gE and autophagy-related (Atg) Atg9/Atg16L1 trafficking pathways. Investigations were carried out with highly purified fractions of VZV virions. When the virion fraction was tested for the presence of autophagy and endosomal proteins, microtubule-associated protein 1 light chain (MAP1LC3B) and Ras-like GTPase 11 (Rab11) were detected. By two-dimensional (2D) and 3D imaging after immunolabeling, both proteins also colocalized with VZV gE in a proportion of cytoplasmic vesicles. When purified VZV virions were enumerated after immunoelectron microscopy, gold beads were detected on viruses following incubation with antibodies to VZV gE (∼100%), Rab11 (50%), and LC3B (30%). Examination of numerous electron micrographs demonstrated that enveloped virions were housed in single-membraned vesicles; viral particles were not observed in autophagosomes. Taken together, our data suggested that some viral particles after secondary envelopment accumulated in a heterogeneous population of single-membraned vesicular compartments, which were decorated with components from both the endocytic pathway (Rab11) and the autophagy pathway (LC3B). The latter cytoplasmic viral vesicles resembled an amphisome. IMPORTANCE VZV infection leads to increased autophagic flux, while inhibition of autophagy leads to a marked reduction in virus spread. In this investigation of the proviral role of autophagy, we found evidence for an intersection of viral exocytosis and autophagy pathways. Specifically, both LC3-II and Rab11 proteins copurified with some infectious VZV particles. The results suggested that a subpopulation of VZV particles were carried to the cell surface in single-walled vesicles with attributes of an amphisome, an organelle formed from the fusion of an endosome and an autophagosome. Our results also addressed the interpretation of autophagy/xenophagy results with mutated herpes simplex virus lacking its ICP34.5 neurovirulence gene (HSVΔ34.5). The VZV genome lacks an ICP34.5 ortholog, yet we found no evidence of VZV particles housed in a double-membraned autophagosome. In other words, xenophagy, a degradative process documented after infection with HSVΔ34.5, was not observed in VZV-infected cells.
منابع مشابه
Varicella-Zoster Virus Infectious Cycle: ER Stress, Autophagic Flux, and Amphisome-Mediated Trafficking
Varicella-zoster virus (VZV) induces abundant autophagy. Of the nine human herpesviruses, the VZV genome is the smallest (~124 kbp), lacking any known inhibitors of autophagy, such as the herpes simplex virus ICP34.5 neurovirulence gene. Therefore, this review assesses the evidence for VZV-induced cellular stress, endoplasmic-reticulum-associated degradation (ERAD), and autophagic flux during t...
متن کاملVaricella Exposure in Neonatal Intensive Care Unit in a Low Resource Country: Successful Prophylaxis with Intravenous Immunoglobulins
Background: Varicella-zoster infection is a serious and potentially fatal disease, especially among newborns.Several studies have described postnatal varicella zoster exposure among neonates and reported on the efficacy of varicella-zoster immunoglobulins (VZIG) used as post-exposure prophylaxis. Unfortunately, VZIG is not available in Jordan. A limited number of studies have investigated the e...
متن کاملCovid-19 Vaccination and Reactivation of Varicella Zoster Virus
Introduction: After COVID-19 pandemic in 2020 that mostly affects upper respiratory tract, the scientists investigated an effective vaccine against the virus. As the vaccination of general population started some patients were visited with varicella zoster virus activation following the COVID vaccine.
متن کاملThe Very Rare Concurrency of Herpes Zoster and Varicella in a 4-Year-Old Boy
Varicella is a common and worldwide disease in childhood. It causes primary (chickenpox) and latent infection that may lead to a reactivation disease called zoster (shingles). Zoster or shingles is caused by reactivation of the virus that has been latent in the spinal dorsal ganglion and may occur even in immunocompetent hosts. Although zoster is rare in children, it ma...
متن کاملSeroepidemiology of varicella zoster virus in healthcare workers in Babol, Northern Iran
Background: Varicella zoster virus (VZV) infection is one of the nosocomial infections and healthcare workers (HCWs) are at high risk group who work in the hospital with likelihood of varicella acquisition or transmission. This study evaluated the VZV seroprevalence in this high risk population in Babol, Iran. Methods: Serological testing for VZV using enzyme linked immunosorbent assay (ELISA)...
متن کامل