This capsid comes into play during infection to attach the virion to specific receptors exposed on the prospective host cell. Capsid proteins are coded by the viral genome.
Due to its limited size, the genome codes for only a few structural proteins besides non-structural regulatory proteins involved in virus replication. Capsids are formed as single or double protein shells and consist of only one or a few structural protein species.
Therefore, multiple protein copies must self assemble to form the continuous three-dimensional capsid structure [ 35 ]. The structural viral proteins are extremely important to the virus, so as to facilitate the transfer of the viral nucleic acid from one host cell to another.
The proteins determine the antigenicity of the virus. There are enveloped Viruses and these envelopes are made up of either lipid or glycoprotein. Lipid envelopes are derived from the host cell. Whereas the envelope glycoproteins are virus encoded. However, there are sugars attached to the viral glycoproteins which often reflect the host cell that harboured the virus. The surface glycoproteins of an enveloped virus attach the virion to a target host cell by properly interacting with a cellular receptor [ 22 ].
Structural biological analysis of viral envelope glycoproteins reveals that viruses have wide range of folds to facilitate their attachment with proper host receptors. Bowden et al. Glycosylated GP trimer is observed in the Lentiviruses of Retroviridae. These semaphorins binds with cell surface receptors to initiate important physiological processes. These observations are made by recent study of viral glycoproteins by employing Macromolecular crystallography [ 10 ].
The M and S proteins of the virus are usually rich in N glycosylated proteins, which have been demonstrated as important virulent factor of viruses [ 98 ]. Thus, E, M and S viral glycoproteins are involved in viral host binding and subsequent virus-host membrane fusion to establish the pathogenesis of the virus. Two envelope glycoproteins, namely E1 and E2 develop the viral spike of the virions of Flaviviridae family [ 61 ] are involved in the engagement with host receptor and conformational change required for membrane fusion Fig.
SARS Coronavirus possess a spike S glycoprotein [ 70 ], which itself performs the membrane fusion for the entry of the virion and its fusion with host cell [ ].
Interestingly, the dengue virus apart from synthesizing the basic capsid, membrane and envelope proteins also produces seven non-structural secretory glycoproteins NS1,2A, 2B, 3, 4A,4B,5 [ 46 ].
These proteins are not integrated in the virus but secreted in the host. Studies have found heterogeneity in the E glycoprotein of Dengue virus [ 56 ]. B cell and T-cell epitopes are predicted in a study by analysing this E glycoprotein [ 46 ].
The Dengue Viral envelope is more ordered than the inner viral core, as the envelope is composed of 90 glycoprotein E dimer icosahedral scaffold [ 58 ]. Computational studies are there to develop vaccines against Dengue virus [ 4 , 97 ].
Distribution of Glycoproteins on the surfaces of different viruses a influenza virus, b SARS Coronavirus, c Hepatitis C virus, d human immunodeficiency virus, e Ebola virus, f Dengue virus and g Chikungunya virus.
There are three glycoproteins present in HIV [ 1 ]; namely gp , gp and gp 41 [ 38 ]. All these are encoded by the ENV gene [ 76 ].
The HIV envelope glycoprotein gp contains nine disulphide bridges and is highly glycosylated, carrying on average 24 N-linked glycans Fig.
Experiments proved that the glycan part of the gp 41 protein has important role in the efficient intracellular transport of another glycoprotein gp Those gp proteins lack gp41 are arrested in golgi complex after their biosynthesis [ 27 ]. Zaire Ebola Virus is the member of Filoviridae group, and the Glycoproteins GP have found to be major pathogenic determinants [ 24 — 26 , 63 , 75 , 99 ].
In the Ebola virion GP gene is the 4th gene among total seven genes in the linear gene order. This synthesizes several proteins. Among them two are predominant. These two proteins are produced due to a furin cleavage of a precursor pre-sGP protein. The GP is actually a Spike protein which is composed of two subunits joined by disulphide linkage Gp1-Gp2 [ 92 ].
The Chikungunya Virus on the other hand are known to produce 4 Non structural glycoproteins nsP [ 91 ] these nsPs have been demonstrated to have important role in keeping the replicase complex of the virus intact in the host as well as to circumvent important host immune responses.
Chikungunya Virus has two envelope proteins, namely E1 and E2 [ 11 ]. Thus, viral glycoproteins have diverse structure and function. Taken together, glycoproteins are important components of the virus structure and each have unique role to establish pathogenesis.
Viral glycoproteins have a definite role in their pathogenesis. The primary goal of viral infection is to identify a receptor on the host cell surface and binding with it. Subsequently this will pave the way of viral entry into the host cell. In most cases, the first attachment site of the virus is a glycan, either a glycoprotein or a glycolipid. So, glycoproteins play a crucial role in viral pathogenesis. The study of glycoproteins in viral infection is most important to know the disease process as well as to develop antiviral treatments.
Glycoprotein—receptor interactions also play important roles in pathogen pattern recognition and in the regulatory signals that control the activities of cells of the immune system. The most important cause behind viral infection is that it has evolved to present its own sugars and receptors in a manner that mimics or interferes with host glycan-based immune functions.
Glycomic studies are ongoing in several viruses. Several advanced technologies are there to decipher structural and functional aspects of glycans like Glycan microarray [ 40 ], Mass Spectrometry and Nano LC. Glycan array represents the actual in vivo interaction in silico. The arrayed multivalent demonstration of polysaccharides mimics the cell surface display.
There are two types of carbohydrate microarray. Those are polysaccharide and oligosaccharide microarray [ 53 ]. Natural polysaccharides are randomly immobilized on solid matrices exploiting hydrophobic physical absorption or charge-based interaction. Polysaccharide microarrays are useful for comparative antigenicity analyses.
Being hydrophilic in nature, oligosaccharides need chemical derivatization before arraying. Through oligosaccharide microarray we can study structure—activity relationships [ 52 ].
Microarrays were developed on maleimide-functionalized surfaces using seven thiol-containing synthetic high-mannose oligosaccharides for the identification of human immunodeficiency virus HIV vaccine candidate antigens [ 2 ].
In case of Influenza glycans, there are protocols for fluorescent labeling of virus, coupling of virus to a glycan microarray, analysis of a glycan microarray slide experiment, and data interpretation. Zhao et al. Finally, through three-dimensional structure characterization, it has been revealed that the role of glycan chain shapes is more important than that of torsion angles [ ]. Though characterization of Glycoproteins is tough but, through Mass Spectrometry, it is now easier to identify structural details of complex glycoproteins.
Mass spectrometry derived glycoproteomics [ ] helps us to precisely identify viral and cellular proteins that are functionally, structurally, and dynamically altered during virus infection, but enables us to identify important proteins having active role in the infection pathway. Additionally, isolation and purification techniques along with quantitative strategies in conjunction with MS significantly improve its sensitivity to detect low-abundant proteins. With time, more virus and host genomes are being sequenced and MS-based glycoproteomics is becoming a very important tool for virology.
A work by Barrientos et al. Another work by Anastassia et al. After Nano-LC the sample is analysed through mass spectrometry. One more work showed that they purified Heat shock protein 90 by NanoLC-MS of Respiratory syncitial virus which have important role in virus particle assembly [ 54 , 80 ].
So it is evident that using these modern techniques, the biological roles of glycoproteins can be studied more conveniently. Virus is a nucleic acid surrounded by proteins. This infective particle is called a virion. In most cases this virion is covered with a fascinating coat composed of glycoproteins through which the virus communicates with its host. The co-evolution of host and virus leads the way of making the glycoprotein coat so fascinating [ 23 ].
It is evident that the infectivity of a virus rather of its nucleic acid is fully dependent on its glycoproteins. Enveloped viruses generally encode membrane proteins and these special proteins are necessary to mediate the specific binding against host cell ligands.
This also directs initial events of membrane fusion and viral internalization. These fascinating envelope proteins are generally glycosylated [ 15 ]. The process of glycosylation takes place in the endoplasmic reticulum ER -Golgi complex secretory pathway. The host cell encoded glycosyl-transferase enzyme catalyses the glycosylation.
This glycosylation is necessary to make the virion host compatible, which is needed by the virus for its pathogenesis. So glycans present at the envelop proteins acts as immunological barriers to resist evasion by the host immune system [ 22 ]. Several Viruses exhibit different glycoproteins on their surface Table 1.
Hepatitis C Virus has two envelope glycoproteins namely E1 and E2 [ 59 , 98 ]. These two proteins play an important role in viral infectivity and can be used as candidate subunit vaccine [ 98 ]. On the other hand, in case of Ebola virus there are glycoproteins GP1 and GP2 which causes cell attachment and cell fusion and therefore the main target of the host antibodies. The Ebola virus has an RNA editing mechanism to regulate these GP 1 and 2 genes which when expressed at high level, disrupts normal cell physiology [ 24 ].
Recent studies proved that several types of glycans in HIV-1 produce different levels in infectivity. Those viruses have more oligomannose and less structural complexity, infects more efficiently. This ultimately proves that mature oligosaccharide structure of the envelope glycans play a pivotal role in the infection process of HIV Due to N -linked glycosylation of gp protein in the endoplasmic reticulum, and further folding and cleaving in the golgi complex; the gp protein of the envelope is produced [ 71 ].
There are two popular glycoproteins present on the surface of Influenza virus namely, Haemaglutinin HA and Neuraminidase NA [ 84 , 88 ]. These are the key molecules for the viral infection which binds with Sialic acid.
Initially, HA binds with sialic acid during the initiation of infection. After viral replication NA degrades its substrate sialic acid to accelerate release of new viruses [ 30 ]. So it is evident from the examples of viruses of diverse family that glycoproteins are the key molecules for a virus to establish an infection within the host and to survive further within the host system. In the study of viral pathogenesis, a special type of glycoprotein, called Semaphorin have been established [ 6 ].
Semaphorins are family of cell surface signaling glycoproteins which binds to the family of plexin glycoprotein cell surface receptors. Semaphorins also activate repulsive guidance pathways having active part in axon guidance, immune regulation and activation, and vascular development [ 57 , 93 ]. Semaphorins have eight known classes. The ectodomains of cellular semaphorins contain C-terminal domain elaborations like PSI plexin, semaphorin and integrin domains, immunoglobulin Ig -like domains, thrombospondin domains and PDZ-domain-binding sites which occassionally attach to the cell-surface.
Whereas the N-terminal having a plexin-binding sema-domain, is conserved in all cases of virus host cell attachment. The sema-domain is the only component found in viruses. Crystallographic studies by Bowden et al. These semaphorins provide a molecular basis for how viruses can optimize their own proteins to override normal physiological interactions. It has been shown epidemiologically that persons with different ABH phenotypes are infected with NoV strains in a genotype-dependant fashion.
An in vitro binding assay using NoV virus-like particles VLPs showed a uniform recognition pattern for type 1 and 2 core structures of histo blood group antigens. NoV VLPs bind more tightly to type 1 carbohydrates than to type 2.
Type 1 carbohydrates are found to be expressed at the surface of the small intestine and targeted by NoV. This property speaks about NoV tissue specificity. So it is evident that glycoproteins perform a major and active role in viral pathogenesis and disease progression. Glycoproteins provide tissue tropism to the virus.
Some virues used to infect the respiratory system whereas some affects the liver. The cause is the type of glycoprotein with which the virus binds to accelerate its invasion. In a study by Raska et al. N -glycosylation of reconbinant gp of HIV1 is varied and affected the recognition by serum antibodies.
Glycosylation of gp protein of HIV1 affects its recognition by neutralizing and non neutralizing monoclonal antibodies. This study also says that this glycosylation is cell specific. Another study by Lin et al. Lin et al.
By modulating N-glycans on Env or glycoprotein during virus production in different primary cells or in the presence of the mannosidase I inhibitor deoxymannojirimycin affected DC-SIGN R infectivity enhancement. So it is evident that virus-producing cell type is a crucial factor in depicting both N-glycan status and virus interactions with DC-SIGN R , which establishes virus tropism and infection within the human body [ 64 ].
Liu et al. Crystallographic studies showed that EV-D68 with sialylated glycan receptor analogues binds on the viral surface. Sialic acid receptor induces a cascade of conformational changes within the virus to secrete a fatty-acid-like molecule which regulates the stability of the virus. So, it is evident that binding of virus to a sialic acid receptor and to immunoglobulin-like receptors facilitates viral entry in enteroviruses. Glycan based viral immunodiagnostics usually have high sensitivity and specificity.
Glycoprotein based IgM serology was developed for the diagnosis of recent primary rubella virus infections and significant sensitivity and specificity was obtained. Similarly, Glycoprotein based serology tests to detect antibodies to herpes simplex virus glycoproteins G-1 and G-2, which evoke a type-specific antibody response have also been developed.
These tests are used to confirm a diagnosis of genital herpes, and also to establish diagnosis of HSV infection in patients with atypical complaints, to identify asymptomatic carriers, and identify persons at risk for acquiring HSV.
Glycan based immunodiagnostics have also been developed for the rapid identification of different strains of Influenza Virus. On the other hand, the main diagnostic challenge related to SARS is to diagnose it differently with atypical pneumonia [ 68 , 79 ].
But all these techniques are extremely sophisticated and of little use in case of epidemics; especially in the developing world. SARS Coronavirus possess a spike S glycoprotein, which itself performs the membrane fusion for the entry of the virion and its fusion with host cell Fig. IgG based diagnostics against this S protein has been developed [ ]. Similarly, as acute Hepatitis C infection is asymptomatic, so it is difficult to diagnose early.
Generally patients come to the clinic with damaged liver. In Tanaka et al. Studies for developing Algorithms confirms Learn More. Sign in via OpenAthens. Sign in via Shibboleth. AccessBiomedical Science. AccessEmergency Medicine. Case Files Collection. Clinical Sports Medicine Collection. Davis AT Collection. Davis PT Collection. Murtagh Collection. About Search. Enable Autosuggest. You have successfully created a MyAccess Profile for alertsuccessName. Home Books Harper's Illustrated Biochemistry, 30e.
Previous Chapter. Next Chapter. Bender D. Bender, David A. Rodwell V. Victor W. Rodwell, et al. For instance, proteoglycan s may be regarded as a subset of glycoproteins since both of them have a protein core.
However, there are differences in several aspects. In structure, glycoproteins have carbohydrate chains attached to a polypeptide side chain whereas proteoglycans have glycosaminoglycan chains attached to the polypeptide. See also:.
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