[PMC free article] [PubMed] [Google Scholar] 55. ability of MVs to infect nectin-1/HVEM-negative CHO-K1 cells suggest a novel way for HSV-1 to spread to and enter target cells. Taken together, our results suggest that HSV-1 could spread through microvesicles to expand its tropism and that microvesicles could shield the virus from neutralizing antibodies as a possible mechanism to escape the host immune response. IMPORTANCE Herpes simplex virus 1 (HSV-1) is a neurotropic pathogen that can infect many types of cells and establishes latent infections in neurons. Extracellular vesicles are a heterogeneous group of membrane vesicles secreted by most cell types. Microvesicles, which are extracellular vesicles which derive from the shedding of the plasma membrane, isolated from the supernatant of HSV-1-infected HOG cells were analyzed to find out whether they were involved in the viral cycle. The importance of our investigation lies in the detection, for the first time, of microvesicles containing HSV-1 virions. In addition, virus-containing microvesicles were endocytosed into CHO-K1 cells and were able to actively infect these otherwise nonpermissive cells. Finally, the infection of CHO cells with these virus-containing microvesicles was BX-912 not completely neutralized by anti-HSV-1 antibodies, suggesting that these extracellular vesicles might shield the virus from neutralizing antibodies as a possible mechanism of immune evasion. KEYWORDS: extracellular vesicles, microvesicles, oligodendrocytes, viral spread, herpes simplex virus INTRODUCTION Herpes simplex virus 1 (HSV-1) is a highly prevalent (1) human pathogen belonging to the neurotropic alphaherpesviruses that can establish latency in neurons (2). After primary infection of epithelial cells, this virus spreads to neurons and establishes latent infections in the trigeminal ganglia. Under certain circumstances, HSV-1 may cause severe pathologies, such as keratoconjunctivitis or encephalitis (3). HSV-1 is also an increasing cause of genital herpes (4, 5). HSV-1 has the ability to enter many different hosts and BX-912 cell BX-912 types (6) using different receptors and different pathways: plasma membrane fusion at neutral pH and low-pH-dependent or low-pH-independent endocytosis (reviewed in references 7 to 10). Regardless of the pathway, HSV glycoproteins, such as the receptor-binding glycoprotein D (gD), the fusion modulator complex gH/gL, and the fusion effector gB, are essential for virion entry. Antibodies (Ab) raised against these glycoproteins may have strong neutralizing activities (11,C13). Regarding maturation and egress, four major stages have been proposed to describe these processes: capsid assembly and DNA packaging in the nucleus; primary envelopment and deenvelopment at the nuclear envelope; tegumentation and secondary envelopment in the cytoplasm; BX-912 and, finally, exocytosis of viral particles at the plasma membrane and/or cell-to-cell transmission at cell junctions (14). A major BX-912 mode of HSV-1 transmission in human tissues is cell-to-cell spread, that is, the direct passage of progeny virus from an infected cell to an adjacent one (15). It is widely accepted that this mechanism of spread represents an immune evasion strategy, since it protects the virus from immune surveillance (15). However, as mentioned above, HSV-1 may use several modes of spread to pass from infected to uninfected cells (7). Many aspects concerning the process of viral spread, for instance, the mechanisms of viral egress from epithelial Rabbit polyclonal to YY2.The YY1 transcription factor, also known as NF-E1 (human) and Delta or UCRBP (mouse) is ofinterest due to its diverse effects on a wide variety of target genes. YY1 is broadly expressed in awide range of cell types and contains four C-terminal zinc finger motifs of the Cys-Cys-His-Histype and an unusual set of structural motifs at its N-terminal. It binds to downstream elements inseveral vertebrate ribosomal protein genes, where it apparently acts positively to stimulatetranscription and can act either negatively or positively in the context of the immunoglobulin k 3enhancer and immunoglobulin heavy-chain E1 site as well as the P5 promoter of theadeno-associated virus. It thus appears that YY1 is a bifunctional protein, capable of functioning asan activator in some transcriptional control elements and a repressor in others. YY2, a ubiquitouslyexpressed homologue of YY1, can bind to and regulate some promoters known to be controlled byYY1. YY2 contains both transcriptional repression and activation functions, but its exact functionsare still unknown cells and spread to neurons and vice versa (16), are not completely understood yet. Clarifying the mechanisms of viral dissemination and subsequent entry into neighboring cells remains a necessary step to understand the viral cycle in the host (7). In this context, secreted vesicles have emerged as a new object of interest for their ability to take part in the intercellular conversation procedure during viral attacks. Extracellular vesicles (EVs) certainly are a extremely heterogeneous band of secreted membrane vesicles.