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Dynamics of virus-receptor interactions in virus binding, signaling, and endocytosis.

Boulant S, Stanifer M, Lozach PY - Viruses (2015)

Bottom Line: During viral infection the first challenge that viruses have to overcome is gaining access to the intracellular compartment.The infection process starts when the virus contacts the surface of the host cell.A complex series of events ensues, including diffusion at the host cell membrane surface, binding to receptors, signaling, internalization, and delivery of the genetic information.

View Article: PubMed Central - PubMed

Affiliation: CellNetworks-Cluster of Excellence and Department of Infectious Diseases, Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany. s.boulant@dkfz-heidelberg.de.

ABSTRACT
During viral infection the first challenge that viruses have to overcome is gaining access to the intracellular compartment. The infection process starts when the virus contacts the surface of the host cell. A complex series of events ensues, including diffusion at the host cell membrane surface, binding to receptors, signaling, internalization, and delivery of the genetic information. The focus of this review is on the very initial steps of virus entry, from receptor binding to particle uptake into the host cell. We will discuss how viruses find their receptor, move to sub-membranous regions permissive for entry, and how they hijack the receptor-mediated signaling pathway to promote their internalization.

No MeSH data available.


Related in: MedlinePlus

Strategies of virus entry. To gain access to the cytoplasm of host cells, viruses can employ two main strategies, i.e., either (A) through endocytosis and escape from endosomal vesicles in a process referred as receptor-mediated endocytosis or (B) by direct penetration from the plasma membrane, referred as endocytosis-independent receptor-mediated entry. Enveloped viruses are shown; however non-enveloped viruses have evolved similar strategies. These are just generalizations and there are exemptions from these rules. Black arrows represent the sequence of events and dashed-red arrows the potential induced signaling.
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viruses-07-02747-f001: Strategies of virus entry. To gain access to the cytoplasm of host cells, viruses can employ two main strategies, i.e., either (A) through endocytosis and escape from endosomal vesicles in a process referred as receptor-mediated endocytosis or (B) by direct penetration from the plasma membrane, referred as endocytosis-independent receptor-mediated entry. Enveloped viruses are shown; however non-enveloped viruses have evolved similar strategies. These are just generalizations and there are exemptions from these rules. Black arrows represent the sequence of events and dashed-red arrows the potential induced signaling.

Mentions: To establish infection and replicate, viruses need to gain access to the intracellular environment. This very first step is strictly dependent on surface exposed cellular receptors to which virus particles bind. Viruses can use two different strategies to enter the host. First, in the classical virus endocytosis model, following binding to one or multiple cellular receptors, virus particles are physically up taken by the endocytic cellular machinery in a process referred to as receptor-mediated endocytosis (Figure 1A). In a second strategy, virus binding to cellular receptors leads to the direct penetration of the virus particles from the plasma membrane, bypassing the endocytic machinery. This process is referred to as endocytosis-independent receptor-mediated entry (Figure 1B). While the receptor-mediated endocytosis model has the merit of being conceptually simple, it is a complex multistep process where viruses are faced with fundamental challenges in order to hijack the host endocytic machinery. First, viruses need to gain access to the cell surface before binding their receptor. This primary attachment is often facilitated by attachment factors that mediate the non-specific binding of virus particles allowing their concentration at the cell surface. These attachments factors are usually small, charged proteins, lipids, or sugar moieties (i.e., heparin sulfate, sialic acid, gangliosides) to which virus particles can bind electrostatically. Following this primary attachment, the virus particles have to interact with the specific virus receptor(s) in order to be internalized. Emerging evidence indicates that cell signaling is strongly activated during viral infection and might facilitate viral uptake and appropriate intracellular targeting [5]. It is often assumed that an active out-in signaling through the receptor molecules triggers the internalization of virus particles by the cellular uptake machinery. Although we have a lot of information on virus/receptor interactions at the molecular and structure level, our understanding of the mechanisms by which virus/receptor interactions induce signaling pathways and how these might actively mediate internalization of the virus/receptor complex is very limited. Conversely, the molecular motifs in a receptor that drive signaling and physical internalization are poorly characterized. Interestingly, several lines of evidence support that all virus/receptor interactions do not always lead to active uptake of the virus particles and that some viruses depend on stochastic uptake by the host cell without relying on active signal induction. Concrete demonstrations that a receptor-mediated signaling results in active virus uptake and productive infection are missing. It is often not clear whether activation of specific cellular signaling pathways drives or results from the endocytic event.


Dynamics of virus-receptor interactions in virus binding, signaling, and endocytosis.

Boulant S, Stanifer M, Lozach PY - Viruses (2015)

Strategies of virus entry. To gain access to the cytoplasm of host cells, viruses can employ two main strategies, i.e., either (A) through endocytosis and escape from endosomal vesicles in a process referred as receptor-mediated endocytosis or (B) by direct penetration from the plasma membrane, referred as endocytosis-independent receptor-mediated entry. Enveloped viruses are shown; however non-enveloped viruses have evolved similar strategies. These are just generalizations and there are exemptions from these rules. Black arrows represent the sequence of events and dashed-red arrows the potential induced signaling.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488714&req=5

viruses-07-02747-f001: Strategies of virus entry. To gain access to the cytoplasm of host cells, viruses can employ two main strategies, i.e., either (A) through endocytosis and escape from endosomal vesicles in a process referred as receptor-mediated endocytosis or (B) by direct penetration from the plasma membrane, referred as endocytosis-independent receptor-mediated entry. Enveloped viruses are shown; however non-enveloped viruses have evolved similar strategies. These are just generalizations and there are exemptions from these rules. Black arrows represent the sequence of events and dashed-red arrows the potential induced signaling.
Mentions: To establish infection and replicate, viruses need to gain access to the intracellular environment. This very first step is strictly dependent on surface exposed cellular receptors to which virus particles bind. Viruses can use two different strategies to enter the host. First, in the classical virus endocytosis model, following binding to one or multiple cellular receptors, virus particles are physically up taken by the endocytic cellular machinery in a process referred to as receptor-mediated endocytosis (Figure 1A). In a second strategy, virus binding to cellular receptors leads to the direct penetration of the virus particles from the plasma membrane, bypassing the endocytic machinery. This process is referred to as endocytosis-independent receptor-mediated entry (Figure 1B). While the receptor-mediated endocytosis model has the merit of being conceptually simple, it is a complex multistep process where viruses are faced with fundamental challenges in order to hijack the host endocytic machinery. First, viruses need to gain access to the cell surface before binding their receptor. This primary attachment is often facilitated by attachment factors that mediate the non-specific binding of virus particles allowing their concentration at the cell surface. These attachments factors are usually small, charged proteins, lipids, or sugar moieties (i.e., heparin sulfate, sialic acid, gangliosides) to which virus particles can bind electrostatically. Following this primary attachment, the virus particles have to interact with the specific virus receptor(s) in order to be internalized. Emerging evidence indicates that cell signaling is strongly activated during viral infection and might facilitate viral uptake and appropriate intracellular targeting [5]. It is often assumed that an active out-in signaling through the receptor molecules triggers the internalization of virus particles by the cellular uptake machinery. Although we have a lot of information on virus/receptor interactions at the molecular and structure level, our understanding of the mechanisms by which virus/receptor interactions induce signaling pathways and how these might actively mediate internalization of the virus/receptor complex is very limited. Conversely, the molecular motifs in a receptor that drive signaling and physical internalization are poorly characterized. Interestingly, several lines of evidence support that all virus/receptor interactions do not always lead to active uptake of the virus particles and that some viruses depend on stochastic uptake by the host cell without relying on active signal induction. Concrete demonstrations that a receptor-mediated signaling results in active virus uptake and productive infection are missing. It is often not clear whether activation of specific cellular signaling pathways drives or results from the endocytic event.

Bottom Line: During viral infection the first challenge that viruses have to overcome is gaining access to the intracellular compartment.The infection process starts when the virus contacts the surface of the host cell.A complex series of events ensues, including diffusion at the host cell membrane surface, binding to receptors, signaling, internalization, and delivery of the genetic information.

View Article: PubMed Central - PubMed

Affiliation: CellNetworks-Cluster of Excellence and Department of Infectious Diseases, Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany. s.boulant@dkfz-heidelberg.de.

ABSTRACT
During viral infection the first challenge that viruses have to overcome is gaining access to the intracellular compartment. The infection process starts when the virus contacts the surface of the host cell. A complex series of events ensues, including diffusion at the host cell membrane surface, binding to receptors, signaling, internalization, and delivery of the genetic information. The focus of this review is on the very initial steps of virus entry, from receptor binding to particle uptake into the host cell. We will discuss how viruses find their receptor, move to sub-membranous regions permissive for entry, and how they hijack the receptor-mediated signaling pathway to promote their internalization.

No MeSH data available.


Related in: MedlinePlus