Virus–receptor interactions play a key regulatory role in viral host range, tissue tropism, and viral pathogenesis. Viruses utilize elegant strategies to attach to one or multiple receptors, overcome the plasma membrane barrier, enter, and access the necessary host cell machinery.
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What is the function of a viral receptor?
The numerous functions of viral receptors all coordinate virus targeting to the correct tissues for infection and crossing cellular barriers, which is necessary for the virus to deliver the genome into the host cell [1].
How does a virus interact with its host cell?
The interaction between a virus and its host cell begins with attachment of the virus particle to specific receptors on the cell surface.
How important are cellular receptors in the pathogenesis of infectious diseases?
Introduction Recognition and interactions with cellular receptors is a critical initial step in the infectious viral life cycle and plays a key regulatory role in host range, tissue tropism, and viral pathogenesis [1].
How does a virus infect a healthy cell?
Viruses have receptors that allow them to attach to healthy (host) cells in your body. Once a virus attaches to and enters a host cell, it can replicate (make copies of itself). The host cell dies, and the virus infects other healthy cells. Sometimes, viruses remain in a host cell without replicating or damaging it.
What is the role of virus receptors in the host cell?
Virus-receptor interactions play a key regulatory role in viral host range, tissue tropism, and viral pathogenesis. Viruses utilize elegant strategies to attach to one or multiple receptors, overcome the plasma membrane barrier, enter, and access the necessary host cell machinery. The viral attachme …
How do viruses interact with their host cells?
The viral attachment protein can be viewed as the "key" that unlocks host cells by interacting with the "lock"-the receptor-on the cell surface , and these lock-and-key interactions are critical for viruses to successfully invade host cells. Many common themes have emerged in virus-receptor utilization within and across virus families demonstrating that viruses often target particular classes of molecules in order to mediate these events. Common viral receptors include sialylated glycans, cell adhesion molecules such as immunoglobulin superfamily members and integrins, and phosphatidylserine receptors. The redundancy in receptor usage suggests that viruses target particular receptors or "common locks" to take advantage of their cellular function and also suggests evolutionary conservation. Due to the importance of initial virus interactions with host cells in viral pathogenesis and the redundancy in viral receptor usage, exploitation of these strategies would be an attractive target for new antiviral therapeutics.
Why is redundancy important in viral receptor usage?
The redundancy in receptor usage suggests that viruses target particular receptors or "common locks" to take advantage of their cellular function and also suggests evolutionary conservation. Due to the importance of initial virus interactions with host cells in viral pathogenesis and the redundancy in viral receptor usage, ...
What is the key to a virus?
The viral attachment protein can be viewed as the "key" that unlocks host cells by interacting with the "lock"-the receptor-on the cell surface, and these lock-and-key interactions are critical for viruses to successfully invade host cells.
What is the key to cellular invasion?
Virus-Receptor Interactions: The Key to Cellular Invasion
What is a virus receptor?
A virus receptor can be defined as a host cell surface component recognized by the virus as a gateway to entry into the cell. Ideally, a virus receptor would fulfill three main characteristics: (1) a physical interaction between the virus and the receptor should be demonstrated; (2) occupying the virus-binding site of the receptor (e.g., with an antibody directed against the receptor, should inhibit virus infection); and (3) the cellular sensitivity to virus infection should correlate with receptor expression. Therefore, cells lacking the receptor should not be infected, and transfection with the gene coding for the receptor would confer sensitivity to infection.
What are the affinities of viral vectors?
These affinities mimic classical ligand (virus)/receptor (host cell) interactions, with the ligand composed of a protein moiety embedded in the topology of the viral capsid (e.g., adenovirus, adeno-associated virus (AAV)) or comprising a domain of a glycoprotein embedded in the viral membrane (e.g., Herpes simplex or lentivirus). Receptor binding stimulates endocytosis of the receptor/virus complex by the host cell through the formation of an endosome budding from the cell membrane.
What is the main receptor for HIV-1?
The CD4 transmembrane protein expressed by a subset of human T-lymphocytes is widely considered as the main receptor for HIV-1. However, CD4 does not fulfill all the characteristics listed. CD4 interacts with the HIV-1 surface envelope glycoprotein gp120 with high affinity 200,201 and some anti-CD4 antibodies, directed against the gp120 binding site, inhibit HIV-1 infection of CD4 + lymphocytes. 70 The ability of HIV-1 to infect several types of CD4-negative cells, including fibroblasts, 202 neural, 203 and intestinal epithelial cells 204 led to the identification of an alternative receptor for HIV-1, the oligodendrocyte differentiation marker GalCer. 79,80 In this respect, HIV-1 behaved as an atypic retrovirus able to use either a protein (CD4) or a glycolipid (GalCer) to gain entry into various cell types.
What is the role of the nucleocapsid in the viral genome?
The viral genome needs to get to the nucleus for the virus that replicates in the nucleus. In other words, the viral nucleocapsid has to overcome two barriers (ie, plasma membrane and nuclear membrane). Compare and contrast the mechanisms by which the viruses penetrate the two membranes.
What are the key components of virus infection?
Virus receptors are key components of the early events involved in cell infection. The examples outlined above should illustrate that the definition of receptors acting solely as attachment molecules is overly simplistic. In addition to attachment, receptors also actively contribute to entry by initiating conformational changes in the virus that lead to uncoating. In addition, they provide mechanisms for internalization – which increasingly appear to involve signaling events that occur upon receptor binding – in which the virus may subvert a natural receptor cycling process. Furthermore, the identification of virus receptors contributes significantly to our understanding of host, tissue, and cell tropism, and helps explain aspects of virus pathogenesis. The selected bibliography provides further examples illustrating aspects of virus receptor identification and function.
Do murine cells express CD4?
Murine fibroblasts do not express CD4 or GalCer and are not sensitive to HIV-1 infection. Therefore, they provided a good model to determine whether the expression of human CD4 in these cells would confer sensitivity to infection. This was not the case. HIV-1 could attach to the surface of murine cells transfected with the gene coding for human CD4, but it was the only property that the transfection conferred. These data suggested that in addition to CD4, auxiliary factors, referred to as fusion cofactors, were required for the postbinding fusion step to ensure the penetration of the virus genome in the host cell. After a long search, the cofactor was identified as fusin,205,206 a G protein-coupled transmembrane receptor that proved to be a member of the family of chemokine receptors. The main coreceptors allowing the postbinding fusion events of HIV-1 were CXCR4 (formerly referred to as fusin) and CCR5. 72 This time, the cotransfection of human CD4 and either CXCR4 or CCR5 conferred to initially resistant cells susceptibility to HIV-1 infection. 205 Independently of these coreceptor studies, Puri et al. showed that metabolic depletion of glycosphingolipid levels in human CD4 + cells rendered these cells incompetent for gp120-dependent fusion. 207 These intriguing data indicated that in addition to the coreceptors, HIV-1 fusion also required a glycolipid. 207 A series of elegant reconstitution experiments demonstrated that the missing element was present in human erythrocyte membranes 207 and was finally identified as the neutral glycosphingolipid Gb 3. 208 The strain-dependent interaction of HIV-1 gp120 with specific glycolipids (chiefly Gb 3 and GM3) provided a biochemical basis to these data and further supported the notion that these glycolipids might serve as fusion cofactors. 78
Does rabies bind to nAChRs?
This suggests that rabies virus binds to nAChRs in the brain, but the pathogenetic significance of this binding in producing neuronal dysfunction in rabies has not yet been established.
What is a viral receptor?
Viral receptors are naturally occurring cellular molecules that serve physiological functions for the cell—functions that have nothing to do with infection. From: Viral Pathogenesis (Third Edition), 2016. Download as PDF. About this page.
What is the role of viral and host interactions in the cell cycle?
The first step, binding to host molecules that serve as viral receptors , is critical in all subsequent events. However, host cell alterations can occur in the virtual absence of entry and infection. These effects are due to viral binding to the cellular receptor and the activation of second messenger systems linked to the receptor.
What is the role of car in the immune system?
Concomitantly with its role as a viral receptor, CAR can also regulate intracellular pathways regulating the immune response without being engaged by viral ligands. For instance, CAR interacts with JAM-L, providing signals for neutrophil transepithelial migration (Zen et al., 2005) ( Figs. 3-i and 7). Like other T cells, epithelial γδ T cells need coreceptor engagement and costimulation for a proper antigen response. γδ T cells express JAM-L at their surface that is responsible for signal transduction. This is leading to cell activation and proliferation upon engagement with CAR, which is found on epithelial cells (Fig. 3 -i). This interaction is mediated by the CAR D1 domain with the membrane proximal Ig domain of JAM-L ( Zen et al., 2005). Soluble CAR is able to bind to JAM-L and induces proliferation and cytokine production by epithelial T cells, in a JAM-L-dependent manner (Witherden et al., 2010). This interaction triggers epithelial γδ T-cell activation, supplying a rapid response to environmental insults (Verdino et al., 2010 ). This epithelial γδ T-cell activation requires PI3K recruitment to JAM-L ICD that will activate downstream effectors for signal transduction ( Verdino et al., 2010; Witherden et al., 2010 ).
What is the role of reoviruses in biology?
Reoviruses provide an excellent model for the study of viral binding which includes biological effects. Furthermore, the as yet unknown structure of the reovirus receptor and its putative biological ligand provides an interesting system in which receptor biological function can be analyzed.
What happens to the envelope of a herpesvirus?
After initial attachment of viral receptor -binding proteins to cell surface proteoglycans followed by specific binding to target cell receptors, the envelope of herpesviruses fuses with the cell membrane. The nucleocapsids cross the cytoplasm to the nuclear membrane; replication of viral DNA and assembly of capsids takes place within the nucleus. With HSV, it is known that the tegument proteins partake in transactivation of the first set of genes. Between 65 and 100 viral proteins are synthesized in an orderly sequence or cascade. Briefly, using HSV as an example, circularization of the herpesvirus genome in the cell nucleus results in the orderly transcription (by host RNA polymerase II) of a cascade of immediate early (IE; α), early (E; β) and late (L; γ) genes. IE proteins activate expression of E genes that include viral-derived enzymes (including DNA polymerase and thymidine kinase (TK)) involved in replication which is thought to proceed in a ‘rolling circle’ manner yielding a concatomer that is cut to genome-length DNA units. Induction by E gene products of L genes results in production of viral structural proteins that package around progeny DNA to give rise to new nucleocapsids.
What is the role of IE proteins in replication?
IE proteins activate expression of E genes that include viral-derived enzymes (including DNA polymerase and thymidine kinase (TK)) involved in replication which is thought to proceed in a ‘rolling circle’ manner yielding a concatomer that is cut to genome-length DNA units.
What are some examples of viral binding?
Several viruses reportedly exploit cellular molecules for binding (see Table 1 ). Two interesting examples are the human immunodeficiency virus (HIV) and the vaccinia virus.
What are the potential side effects of antivirals?
Side effects from antivirals vary depending on the drug type and strength (dosage). You may experience:
Why are antivirals more challenging to develop?
Each antiviral only works against a specific virus. Because viruses inside cells are harder to target, antiviral drugs are more challenging to develop. There are more viruses than antiviral drugs to treat them.
What are antivirals?
Antivirals are medications that help your body fight off certain viruses that can cause disease. Antiviral drugs are also preventive. They can protect you from getting viral infections or spreading a virus to others.
What are viruses?
Viruses are tiny (microscopic) infectious agents that grow and multiply only inside living cells of an organism. Viruses have receptors that allow them to attach to healthy (host) cells in your body. Once a virus attaches to and enters a host cell, it can replicate (make copies of itself). The host cell dies, and the virus infects other healthy cells.
How do antiviral medications work?
Antiviral medicines work differently depending on the drug and virus type. Antivirals can:
How do you take antiviral medications?
Most antivirals are oral drugs that you swallow. But you may also receive antiviral medications as:
How long do you need to take antiviral drugs?
Treatment length varies depending on the antiviral drug and viral infection. You may need one dose of an IV drug or a week of oral medicine.
What is the innate immune response?
Introduction to the Innate Immune Response. The innate immune response forms the first line of defense against invading pathogens. Innate immunity includes barriers and a variety of cells and molecules that are part of the rapid response to threats to our health.
Why is it important to understand how immunity works?
Understanding how immunity works is important for making sense of the news around the risk, spread, and treatment of diseases like COVID-19 ...
What is an innate immunity?
Innate immunity can help protect us from a variety of pathogens, including the coronavirus that causes COVID-19, though the specifics and the efficacy of the response can differ depending on the type of pathogen. Full Screen. 1 2 3 4 5 6 7 8 9 10 11 12 13.
Which cells are part of the adaptive immune system?
The antibodies produced by B cells form part of the adaptive immune response and can recognize almost any molecule that might invade the body. In addition, there is a second branch to the adaptive immune system called cellular immunity. T cells form the basis of cellular immunity and can very specifically kill cells that have been infected by viruses. This video compares the two branches of the adaptive immune response, with a particular emphasis on the antiviral effects of T cells. This video features HMX Fundamentals Immunology faculty member Shiv Pillai of Harvard Medical School.
Do T cells respond to viruses?
While the innate immune and B cell responses are effective against a wide variety of pathogens, T cells can respond very specifically to intracellular pathogens, such as viruses. In this interactive, you will walk through an example of a T cell response to a viral invasion, as would occur in the case of COVID-19. Full Screen.
