Viruses exploit the tissue physiology of the host to spread in vivo

Sewald, Xaver; Motamedi, Nasim; Mothes, Walther

doi:10.1016/j.ceb.2016.04.008

Cited by 21 publications

(26 citation statements)

References 131 publications

(98 reference statements)

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“…Our findings corroborate several reports on how microbial pathogens may manipulate signaling pathways of the host cells, particularly cytoskeletal dynamics, to help them invade, replicate and maintain infections (Chazal and Gerlier, 2003 ; Sewald et al, 2016 ). Thus, IQGAP1 regulates egress of Ebola virus (Lu et al, 2013 ), invasion and replication of Moloney leukemia virus (Leung et al, 2006 ) and virulence of swine fever virus (Gladue et al, 2011 ).…”

Section: Discussionsupporting

confidence: 91%

“…A large group of proteins is required for regulation of cell morphology, migration, differentiation, proliferation and apoptosis (Table 1 , shown in green). Indeed, virus can target and manipulate host cytoskeleton dynamics and organization which may ensure virus replication and spread (Sewald et al, 2016 ). Dendritic cells (Cunningham et al, 2010 ), monocytes (Daley-Bauer et al, 2014 ), and T-cells (Murooka et al, 2012 ) can be hijacked by varicella zoster virus, cytomegalovirus and HIV, and thereby used as migratory vehicles for viral dissemination.…”

Section: Discussionmentioning

confidence: 99%

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Perturbation of Wound Healing, Cytoskeletal Organization and Cellular Protein Networks during Hazara Virus Infection

Molinas

Turkina

Magnusson

et al. 2017

Front. Cell Dev. Biol.

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Normal epithelial and endothelial renewal and healing after bacterial and viral challenges are essential for homeostasis along the intestine and the blood and lymphatic vessels. We thus investigated whether and how virus affects migration of human epithelial cells and specifically how the nucleocapsid protein (N) modulates the cellular proteome and interactome using human Caco-2 cells in a wound-healing assay with Hazara virus as a model. Here, Hazara virus blocked cell migration in a dose- and time-dependent manner, disrupted the actin cytoskeleton and specifically reduced the expression of the IQ-motif-containing GTPase-activating protein 1 (IQGAP1) and water channel aquaporin 6 (AQP6) that regulate cytoskeletal organization, water homeostasis and vesicle communication. Moreover, in the Caco-2 cell proteome, we identified several distinct groups of molecules associating with N upon Hazara virus infection, being involved in the ensemble of important cellular processes, e.g., chaperone activity, metabolism, cellular defense against infections, cell morphology, and migration. These events do not only facilitate the virus life cycle, but they are also crucial for membrane and cytoskeleton dynamics, cellular self-renewal and wound healing, being so essential for body integrity and homeostasis.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Perturbation of Wound Healing, Cytoskeletal Organization and Cellular Protein Networks during Hazara Virus Infection

Molinas

Turkina

Magnusson

et al. 2017

Front. Cell Dev. Biol.

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“…Next, the assembly and egress of the viral progeny become polarized toward contact sites. For HIV, integrins and intercellular adhesion molecules surround virological synapses, and polarization of virus assembly is directed by the rearrangement of the cytoskeleton and the secretory machinery (32). Viruses that use actin polymerization as a driving force for spread include murine leukemia virus and vaccinia virus (30).…”

mentioning

confidence: 99%

Cell-to-Cell Transmission Is the Main Mechanism Supporting Bovine Viral Diarrhea Virus Spread in Cell Culture

Merwaiss

Czibener

Álvarez

2019

J Virol

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After initiation of an infective cycle, spread of virus infection can occur in two fundamentally different ways: (i) viral particles can be released into the external environment and diffuse through the extracellular space until they interact with a new host cell, and (ii) virions can remain associated with infected cells, promoting the direct passage between infected and uninfected cells that is referred to as direct cell-to-cell transmission. Although evidence of cell-associated transmission has accumulated for many different viruses, the ability of members of the genus Pestivirus to use this mode of transmission has not been reported. In the present study, we used a novel recombinant virus expressing the envelope glycoprotein E2 fused to mCherry fluorescent protein to monitor the spreading of bovine viral diarrhea virus (BVDV) (the type member of the pestiviruses) infection. To demonstrate direct cell-to-cell transmission of BVDV, we developed a cell coculture system that allowed us to prove direct transmission from infected to uninfected cells in the presence of neutralizing antibodies. This mode of transmission requires cell-cell contacts and clathrin-mediated receptor-dependent endocytosis. Notably, it overcomes antibody blocking of the BVDV receptor CD46, indicating that cell-to-cell transmission of the virus involves the engagement of coreceptors on the target cell. IMPORTANCE BVDV causes one of the most economically important viral infections for the cattle industry. The virus is able to cross the placenta and infect the fetus, leading to the birth of persistently infected animals, which are reservoirs for the spread of BVDV. The occurrence of persistent infection has hampered the efficacy of vaccination because it requires eliciting levels of protection close to sterilizing immunity to prevent fetal infections. While vaccination prevents disease, BVDV can be detected if animals with neutralizing antibodies are challenged with the virus. Virus cell-to-cell transmission allows the virus to overcome barriers to free virus dissemination, such as antibodies or epithelial barriers. Here we show that BVDV exploits cell-cell contacts to propagate infection in a process that is resistant to antibody neutralization. Our results provide new insights into the mechanisms underlying the pathogenesis of BVDV infection and can aid in the design of effective control strategies.

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“…Various types of synapses also exist for the vertebrate immune system cells (immune synapses), which either synapse with each other or with tumor or infected cells (reviewed by Alcover et al, 2016). Interestingly, recent research has shown that human immunodeficiency virus can propagate by inducing, in addition to TNT, filopodia formation between infected and uninfected cells (Sherer and Mothes, 2008); this is also considered to be a synaptic process (virological synapses) (reviewed by Sewald et al, 2016;Dufloo et al, 2018). The morphogenetic synapsis (reviewed by Kornberg, 2017) could be envisioned as part of an evolutionarily conserved mechanism for cellular communication that supports cell-cell signaling in diverse biological contexts.…”

Section: Discussionmentioning

confidence: 99%

The cytoneme connection: direct long-distance signal transfer during development

2019

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During development, specialized cells produce signals that distribute among receiving cells to induce a variety of cellular behaviors and organize tissues. Recent studies have highlighted cytonemes, a type of specialized signaling filopodia that carry ligands and/or receptor complexes, as having a role in signal dispersion. In this Primer, we discuss how the dynamic regulation of cytonemes facilitates signal transfer in complex environments. We assess recent evidence for the mechanisms for cytoneme formation, function and regulation, and postulate that contact between cytoneme membranes promotes signal transfer as a new type of synapse (morphogenetic synapsis). Finally, we reflect on the fundamental unanswered questions related to understanding cytoneme biology.

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Viruses exploit the tissue physiology of the host to spread in vivo

Cited by 21 publications

References 131 publications

Perturbation of Wound Healing, Cytoskeletal Organization and Cellular Protein Networks during Hazara Virus Infection

Perturbation of Wound Healing, Cytoskeletal Organization and Cellular Protein Networks during Hazara Virus Infection

Cell-to-Cell Transmission Is the Main Mechanism Supporting Bovine Viral Diarrhea Virus Spread in Cell Culture

The cytoneme connection: direct long-distance signal transfer during development

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