RNA editing in members of the Ebolavirus genus increases their genome coding capacity by producing multiple transcripts encoding variants of structural and nonstructural glycoproteins from a single gene, ultimately increasing its ability for host adaptation. Also observed in many cellular organisms, alternative splicing allows production of transcripts having the potential to encode different proteins with different functions from the same gene Fig.
The sequence of the mRNA is not changed as with RNA editing; rather the coding capacity is changed as a result of alternative splice sites. Alternative splicing is regulated by cellular and viral proteins that modulate the activity of the splicing factors U1 and U2, both of which are components of the spliceosome. Activation of the spliceosome is facilitated by cis-acting signals in the mRNA sequence.
While only mature, spliced mRNA transcripts are exported out of the nucleus, hepadnaviruses and retroviruses are able to export nonspliced mRNA transcripts out of the nucleus for translation. On the other hand, the NS1 protein n onstructural p rotein 1 of influenza viruses can interact with multiple host cellular factors via its effector- and RNA-binding domains.
It is capable of associating with numerous cellular spliceosome subunits, such as U1 and U6 snRNAs, and can inhibit cellular gene expression by blocking the spliceosome component recruitment and its transition to the active state. Alternative splicing. Alternative splicing is common in parvovirus pre-mRNA transcript processing and allows for the generation of different proteins from a specific nucleotide sequence on the viral mRNA strand.
Dotted lines indicate alternative splice sites. Therefore, viruses can induce preferential induction of viral mRNA splicing by the cellular splicing machinery. Knowledge concerning the coordination between cellular and viral genome splicing comes from adenoviruses and retroviruses, but only limited data are available for other viruses, for example, influenza viruses. This is also referred to as stop codon read-through, and is a programmed cellular and viral-mediated mechanism used to produce C-terminally extended polypeptides, and in viruses, it is often used to express replicases.
Termination of translation occurs when one of three stop codons enters the A-site of the small 40S ribosomal subunit. Stop codons are recognized by release factors eRF1 and eRF3 , which promote hydrolysis of the peptidyl-tRNA bond in the peptidyl transferase center P-site of the large ribosomal subunit.
Read-through occurs when this leaky stop codon is misread as a sense codon with translation continuing to the next termination codon. Read-through signals and mechanisms of prokaryotic, plant, and mammalian viruses are variable and are still poorly understood.
Programmed ribosomal frameshifting is a tightly controlled, programmed strategy used by some viruses to produce different proteins encoded by two or more overlapping open reading frames Fig. Ordinarily, ribosomes function to maintain the reading frame of the mRNA sequence being translated. However, some viral mRNAs carry specific sequence information and structural elements in their mRNA molecules that cause ribosomes to slip, and then readjust the reading frame.
This ribosomal frameshift enables viruses to encode more proteins in spite of their small size. Ribosomal frameshifting. This occurs because the initiation codon can be part of a weak Kozak consensus sequence. As a result, there can be the production of several different proteins if the AUG codon is not in frame, or proteins with different N-termini if the AUGs are in the same frame.
A number of viruses engage in leaky scanning, including members of the families Herpesviridae , Orthomyxoviridae , and Reoviridae. It is, therefore, referred to as cap-dependent discontinuous scanning. The mechanism of ribosome shunting has not been described in molecular detail. Shunting expands the coding capacity of mRNAs of viruses such as caulimoviruses. Ribosomal shunting. Ribosomes, therefore, skip the synthesis of the glycyl-prolyl peptide bond at the C-terminus of a 2A peptide cleavage of the peptide bond between a 2A peptide and its immediate downstream peptide.
Translation is then reinitiated on the same codon, which leads to production of two individual proteins from one open reading frame. Viruses not only employ strategies that maximize the coding capacity of their small genomes, disguise their mRNA with the same structural elements found in host mRNA, regulate their genome expression in a time- and space-dependent manner, but they have also evolved ways of subverting host cell functions in order to favor their own replication and translation.
These phosphorylation events serve to activate or deactivate the enzyme. Some viruses herpesviruses, bunyaviruses counteract this phosphorylation at serine amino acids to inactivate RNA polymerase, while other viruses orthomyxviruses, togaviruses disrupt cellular RNA polymerase function by signaling ubiquitination of the enzyme and its subsequent degradation by proteasomal action.
Phosphorylation of serine residues located on the CTD of the enzymes is blocked by some viruses. Other viruses arrest RNA Pol activity by signaling ubiquitination of the transcribing enzyme, which is subsequently degraded by the proteasome.
Viruses can engage in targeted disruption of cellular mRNA export pathways to promote preferential viral gene expression Fig. All DNA viruses replicate within the nucleus except poxviruses, asfarviruses, and phycodnaviruses. Few RNA viruses, including bornaviruses, orthomyxoviruses, and retroviruses, replicate in the nucleus. Trafficking between the nucleus and cytoplasm is usually unidirectional for large macromolecules like the mRNA transcript, and occurs through the n uclear p ore c omplex NPC.
Viruses that replicate in the nucleus must out-compete cellular mRNAs to export viral mRNAs out of the nucleus for translation into virus gene products in the cytoplasm. Several viruses can inhibit nuclear export of cellular mRNAs by disrupting nuclear export receptors exportin1 and TIP-associated protein and nucleoporins that comprise the NPC to compromise their function in nucleocytoplasmic trafficking of cellular mRNA.
One half of the NPC is shown in the diagram. Many DNA viruses e. Viruses have developed different strategies to effectively degrade host mRNAs and to allow preferential translation of their own mRNA Fig.
Most viruses produce an endonuclease that cleaves host mRNAs, which are then degraded by host exonucleases e. Betacoronaviruses, influenza viruses, vaccinia viruses, and herpesviruses can produce viral endonucleotyic products to an extent that saturates cellular RNA decay-related quality control mechanisms and limit their function.
Transcripts of cytoplasmic viruses must circumvent the cellular mRNA decay machinery to enable virion production. Picornaviruses are able to suppress cellular RNA decay factors, and polioviruses and human rhinoviruses produce viral proteases that degrade Xrn1, Dcp1, Dcp2, Pan3 a deadenylase , and AUF1decay factors. Viruses capable of inducing the shutdown of cellular mRNA translation are able to continue to translate at least part of their mRNAs using noncanonical translation mechanisms, for example, cap-independent translation, ribosome shunting, and leaking scanning e.
Shutoff of host translation machinery by viral interference with specific eukaryotic translation initiation factors and poly A binding protein PABP. Most viruses interact with cellular chaperones in order to ensure correct folding of viral proteins. Viral proteins often consist of multiple domains or are produced as polyprotein precursors, which must be processed before they can be functional.
The coat protein or capsid is a meta-stable structure that must be specifically assembled in a preordered arrangement without reaching minimum free energy; yet must be disassembled upon entry of the host cell. Some cellular chaperones, for example, Hsp70, are used to accelerate the maturation of viral proteins and are involved in regulating the viral biological cycle.
The high rate of mutation in RNA viruses may mean an increased dependency on chaperones for the gene products of these viruses. Hsp70 can refold denatured proteins, which negates some of the destabilizing alterations in structural proteins as a result of mutated genes. This ensures that a high proportion of viral proteins is accurately configured to function in virus multiplication. Viruses can manipulate the cellular metabolism to provide an increased pool of molecules, for example, nucleotides and amino acids, which are required for viral gene expression and virion assembly.
Some viruses need to create a lipid-rich intracellular environment favorable for their replication, morphogenesis, and egress. Replication of HCV occurs on specific lipid raft domains, whereas assembly occurs in lipid droplets. As such, in order for HCV to create replication compartments and increase sites of assembly, the RNA virus requires both the synthesis of fatty acids, for example, cholesterol, sphingolipids, phosphatidylcholine, and phosphatidylethanolamine, and formation of lipid droplets.
Lipids are especially required for assembly of virions of enveloped viruses as these molecules are a major component of membranes.
Cellular lipid metabolism is affected at three levels: enhanced lipogenesis, impaired degradation, and disruption of export, which is subsequently manifested in the host as HCV-associated pathogenesis. Viral interference of the host cell cycle can result in the dysregulation of cell cycle checkpoint control mechanisms to promote viral replication and to facilitate efficient virion assembly.
Both DNA and RNA viruses specifically encode proteins responsible for targeting and arresting essential cell cycle regulators to create intracellular conditions that are favorable for viral replication and propagation.
Retroviruses and other RNA viruses also interfere with the host cell cycle. Viral-mediation of the cell cycle can increase the efficiency of viral gene expression and virion assembly. Cell cycle arrest may delay apoptosis of infected cells.
Many viruses encode a cyclin-D homolog protein v-cyclin that associates with Cdk6 to phosphorylate Rb, which regulates G1 phase. Various DNA viruses primarily infect quiescent or differentiated cells, which contain low levels of deoxynucleotides dNTPs as these cells do not undergo active cell division.
As such, a restricted pool of dNTPs will not provide an ideal environment for viral replication. It has been proposed that such viruses can induce quiescent cells to enter the cell cycle, specifically the S phase, in order to create an environment that generates factors, such as nucleotides, that are required for viral replication.
Large DNA viruses, for example, herpesviruses, can cause cell cycle arrest as a mean of competing for cellular DNA replication resources. The viral-mediated modifications of host cell cycles, which may be detrimental to cellular physiology, significantly contributes to associated pathologies, such as cancer progression and cell transformation. A summary of most of the strategies developed by viruses to ensure viral replication and gene expression is provided in Fig. Summary of strategies developed by viruses to ensure viral replication and gene expression.
Finally, viruses have developed a number of targeted strategies to manipulate cellular activities, which enable specific recruitment of macromolecules required for viral replication and gene expression at specific locations in the host cell. Typically, these macromolecules are recruited and concentrated into specific cytoplasmic or nuclear compartments.
Formation of such specialized cellular microenvironments, also termed viroplasms, virus factories, virus replication centers, complexes, or compartments, requires the coordinated control of cellular biosynthesis in addition to 1 alterations in the dynamics and distribution of the cytoskeleton and associated motor proteins, 2 relocalization of cellular organelles, and 3 reorganization and redeployment of cellular membranes associated with membrane-bound organelles, for example, the endoplasmic reticulum, mitochondria, chloroplasts, Golgi apparatus, endosomes, and lysosomes in eukaryotes.
In addition, DNA viruses that replicate in the nucleus induce nuclear reorganization and redistribution of chromatin and nuclear domain components such as the nucleolus, interchromatin granules, and Cajal bodies.
These compartments provide a scaffold for efficient viral gene expression, while simultaneously concealing viral genomes refer to Chapter Host—Virus Interactions: Battles Between Viruses and Their Hosts and their products from immunological detection.
National Center for Biotechnology Information , U. Published online Mar Sephra Rampersad 1 and Paula Tennant 2. Author information Copyright and License information Disclaimer. Augustine, Trinidad and Tobago. All rights reserved. Coronavirus particles contain four main structural proteins. Homotrimers of the virus encoded S protein make up the distinctive spike structure on the surface of the virus [ 4 , 5 ]. The trimeric S glycoprotein is a class I fusion protein [ 6 ] and mediates attachment to the host receptor [ 7 ].
In most, coronaviruses, S is cleaved by a host cell furin-like protease into two separate polypeptides noted S1 and S2 [ 8 , 9 ]. S1 makes up the large receptor-binding domain of the S protein, while S2 forms the stalk of the spike molecule [ 10 ]. The M protein is the most abundant structural protein in the virion.
It has a small N-terminal glycosylated ectodomain and a much larger C-terminal endodomain that extends 6—8 nm into the viral particle [ 12 ]. Despite being co-translationally inserted in the ER membrane, most M proteins do not contain a signal sequence. Recent studies suggest the M protein exists as a dimer in the virion, and may adopt two different conformations, allowing it to promote membrane curvature as well as to bind to the nucleocapsid [ 13 ].
The coronavirus E proteins are highly divergent but have a common architecture [ 14 ]. The membrane topology of E protein is not completely resolved but most data suggest that it is a transmembrane protein. The E protein has an N-terminal ectodomain and a C-terminal endodomain and has ion channel activity. As opposed to other structural proteins, recombinant viruses lacking the E protein are not always lethal, although this is virus type dependent [ 15 ].
The E protein facilitates assembly and release of the virus see Subheading 4. For instance, the ion channel activity in SARS-CoV E protein is not required for viral replication but is required for pathogenesis [ 16 ]. The N protein constitutes the only protein present in the nucleocapsid. It has been suggested that optimal RNA binding requires contributions from both domains [ 17 , 18 ].
N protein is also heavily phosphorylated [ 19 ], and phosphorylation has been suggested to trigger a structural change enhancing the affinity for viral versus nonviral RNA. N protein binds the viral genome in a beads-on-a-string type conformation. The genomic packaging signal has been found to bind specifically to the second, or C-terminal RNA binding domain [ 22 ].
N protein also binds nsp3 [ 18 , 23 ], a key component of the replicase complex, and the M protein [ 24 ]. These protein interactions likely help tether the viral genome to the replicase—transcriptase complex RTC , and subsequently package the encapsidated genome into viral particles.
The protein acts as a hemagglutinin, binds sialic acids on surface glycoproteins, and contains acetyl-esterase activity [ 25 ]. These activities are thought to enhance S protein-mediated cell entry and virus spread through the mucosa [ 26 ]. Interestingly, HE enhances murine hepatitis virus MHV neurovirulence [ 27 ]; however, it is selected against in tissue culture for unknown reasons [ 28 ].
The initial attachment of the virion to the host cell is initiated by interactions between the S protein and its receptor. The S-protein—receptor interaction is the primary determinant for a coronavirus to infect a host species and also governs the tissue tropism of the virus. Many coronaviruses utilize peptidases as their cellular receptor. It is unclear why peptidases are used, as entry occurs even in the absence of the enzymatic domain of these proteins. Following receptor binding, the virus must next gain access to the host cell cytosol.
This is generally accomplished by acid-dependent proteolytic cleavage of S protein by a cathepsin, TMPRRS2 or another protease, followed by fusion of the viral and cellular membranes.
Fusion generally occurs within acidified endosomes, but some coronaviruses, such as MHV, can fuse at the plasma membrane. The formation of this bundle allows for the mixing of viral and cellular membranes, resulting in fusion and ultimately release of the viral genome into the cytoplasm. The next step in the coronavirus lifecycle is the translation of the replicase gene from the virion genomic RNA.
The replicase gene encodes two large ORFs, rep1a and rep1b, which express two co-terminal polyproteins, pp1a and pp1ab Fig. In most cases, the ribosome unwinds the pseudoknot structure, and continues translation until it encounters the rep1a stop codon.
Occasionally the pseudoknot blocks the ribosome from continuing elongation, causing it to pause on the slippery sequence, changing the reading frame by moving back one nucleotide, a -1 frameshift, before the ribosome is able to melt the pseudoknot structure and extend translation into rep1b, resulting in the translation of pp1ab [ 32 , 33 ].
It is unknown exactly why these viruses utilize frameshifting to control protein expression, but it is hypothesized to either control the precise ratio of rep1b and rep1a proteins or delay the production of rep1b products until the products of rep1a have created a suitable environment for RNA replication [ 34 ]. Polyproteins pp1a and pp1ab contain the nsps 1—11 and 1—16, respectively. In pp1ab, nsp11 from pp1a becomes nsp12 following extension of pp1a into pp1b.
These polyproteins are subsequently cleaved into the individual nsps [ 35 ]. Coronaviruses encode either two or three proteases that cleave the replicase polyproteins. They are the papain-like proteases PLpro , encoded within nsp3, and a serine type protease, the main protease, or Mpro, encoded by nsp5.
Next, many of the nsps assemble into the replicase—transcriptase complex RTC to create an environment suitable for RNA synthesis, and ultimately are responsible for RNA replication and transcription of the sub-genomic RNAs. Interestingly, ribonucleases nspNendoU and nspExoN activities are unique to the Nidovirales order and are considered genetic markers for these viruses [ 37 ]. Viral RNA synthesis follows the translation and assembly of the viral replicase complexes.
Sub-genomic RNAs serve as mRNAs for the structural and accessory genes which reside downstream of the replicase polyproteins. Both genomic and sub-genomic RNAs are produced through negative-strand intermediates. Many cis-acting sequences are important for the replication of viral RNAs.
Therefore, these different structures are proposed to regulate alternate stages of RNA synthesis, although exactly which stages are regulated and their precise mechanism of action are still unknown. Perhaps the most novel aspect of coronavirus replication is how the leader and body TRS segments fuse during production of sub-genomic RNAs.
This was originally thought to occur during positive-strand synthesis, but now it is largely believed to occur during the discontinuous extension of negative-strand RNA [ 48 ]. However, many questions remain to fully define the model. Answers to these questions and others will be necessary to gain a full perspective of how RNA replication occurs in coronaviruses. Finally, coronaviruses are also known for their ability to recombine using both homologous and nonhomologous recombination [ 50 , 51 ].
The ability of these viruses to recombine is tied to the strand switching ability of the RdRp. Following replication and sub-genomic RNA synthesis, the viral structural proteins, S, E, and M are translated and inserted into the endoplasmic reticulum ER. These proteins move along the secretory pathway into the endoplasmic reticulum—Golgi intermediate compartment ERGIC [ 52 , 53 ].
There, viral genomes encapsidated by N protein bud into membranes of the ERGIC containing viral structural proteins, forming mature virions [ 54 ]. The M protein directs most protein—protein interactions required for assembly of coronaviruses.
However, M protein is not sufficient for virion formation, as virus-like particles VLPs cannot be formed by M protein expression alone. When M protein is expressed along with E protein VLPs are formed, suggesting these two proteins function together to produce coronavirus envelopes [ 55 ]. The S protein is incorporated into virions at this step, but is not required for assembly.
While the M protein is relatively abundant, the E protein is only present in small quantities in the virion. Thus, it is likely that M protein interactions provide the impetus for envelope maturation. It is unknown how E protein assists M protein in assembly of the virion, and several possibilities have been suggested. Some work has indicated a role for the E protein in inducing membrane curvature [ 57 — 59 ], although others have suggested that E protein prevents the aggregation of M protein [ 60 ].
The E protein may also have a separate role in promoting viral release by altering the host secretory pathway [ 61 ]. The M protein also binds to the nucleocapsid, and this interaction promotes the completion of virion assembly. However, it is unclear exactly how the nucleocapsid complexed with virion RNA traffics to the ERGIC to interact with M protein and become incorporated into the viral envelope.
Another outstanding question is how the N protein selectively packages only positive-sense full-length genomes among the many different RNA species produced during infection. A packaging signal for MHV has been identified in the nsp15 coding sequence, but mutation of this signal does not appear to affect virus production, and a mechanism for how this packaging signal works has not been determined [ 22 ].
Furthermore, most coronaviruses do not contain similar sequences at this locus, indicating that packaging may be virus specific. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis. It is not known if the virions use the traditional pathway for transport of large cargo from the Golgi or if the virus has diverted a separate, unique pathway for its own exit.
In several coronaviruses, S protein that does not get assembled into virions transits to the cell surface where it mediates cell—cell fusion between infected cells and adjacent, uninfected cells. This leads to the formation of giant, multinucleated cells, which allows the virus to spread within an infected organism without being detected or neutralized by virus-specific antibodies.
Coronaviruses cause a large variety of diseases in animals, and their ability to cause severe disease in livestock and companion animals such as pigs, cows, chickens, dogs, and cats led to significant research on these viruses in the last half of the twentieth century.
PEDV recently emerged in North America for the first time, causing significant losses of young piglets.
Porcine hemagglutinating encephalomyelitis virus PHEV mostly leads to enteric infection but has the ability to infect the nervous system, causing encephalitis, vomiting, and wasting in pigs. Feline enteric coronavirus FCoV causes a mild or asymptomatic infection in domestic cats, but during persistent infection, mutation transforms the virus into a highly virulent strain of FCoV, Feline Infectious Peritonitis Virus FIPV , that leads to development of a lethal disease called feline infectious peritonitis FIP.
FIP has wet and dry forms, with similarities to the human disease, sarcoidosis. However, additional research is needed to confirm this hypothesis. Bovine CoV causes significant losses in the cattle industry and also has spread to infect a variety of ruminants, including elk, deer, and camels. Infection of the reproductive tract with IBV significantly diminishes egg production, causing substantial losses in the egg-production industry each year [ 63 ].
More recently, a novel coronavirus named SW1 has been identified in a deceased Beluga whale [ 64 ]. Large numbers of virus particles were identified in the liver of the deceased whale with respiratory disease and acute liver failure.
Although, electron microscopic images were not sufficient to identify the virus as a coronavirus, sequencing of the liver tissue clearly identified the virus as a coronavirus. Finally, another novel family of nidoviruses, Mesoniviridae , has been recently identified as the first nidoviruses to exclusively infect insect hosts [ 66 , 67 ].
These viruses are highly divergent from other nidoviruses but are most closely related to the roniviruses. Interestingly, these viruses do not encode for an endoribonuclease, which is present in all other nidoviruses. These attributes suggest these viruses are the prototype of a new nidovirus family and may be a missing link in the transition from small to large nidoviruses. The most heavily studied animal coronavirus is murine hepatitis virus MHV , which causes a variety of outcomes in mice, including respiratory, enteric, hepatic, and neurologic infections.
These infections often serve as highly useful models of disease. Interestingly, MHV-3 induces cellular injury through the activation of the coagulation cascade [ 68 ]. Most notably, A59 and attenuated versions of JHMV cause a chronic demyelinating disease that bears similarities to multiple sclerosis MS , making MHV infection one of the best models for this debilitating human disease.
Early studies suggested that demyelination was dependent on viral replication in oligodendrocytes in the brain and spinal cord [ 69 , 70 ]; however, more recent reports clearly demonstrate that the disease is immune-mediated. Irradiated mice or immunodeficient lacking T and B cells mice do not develop demyelination, but addition of virus-specific T cells restores the development of demyelination [ 71 , 72 ].
Additionally, demyelination is accompanied by a large influx of macrophages and microglia that can phagocytose infected myelin [ 73 ], although it is unknown what the signals are that direct immune cells to destroy myelin.
These factors make MHV an ideal model for studying the basics of viral replication in tissue culture cells as well as for studying the pathogenesis and immune response to coronaviruses. Prior to the SARS-CoV outbreak, coronaviruses were only thought to cause mild, self-limiting respiratory infections in humans.
They cause more severe disease in neonates, the elderly, and in individuals with underlying illnesses, with a greater incidence of lower respiratory tract infection in these populations. HCoV-NL63 is also associated with acute laryngotracheitis croup [ 79 ]. One interesting aspect of these viruses is their differences in tolerance to genetic variability. HCoVE isolates from around the world have only minimal sequence divergence [ 80 ], while HCoV-OC43 isolates from the same location but isolated in different years show significant genetic variability [ 81 ].
Based on the ability of MHV to cause demyelinating disease, it has been suggested that human CoVs may be involved in the development of multiple sclerosis MS. However, no evidence to date suggests that human CoVs play a significant role in MS. It is the most severe human disease caused by any coronavirus.
The outbreak began in a hotel in Hong Kong and ultimately spread to more than two dozen countries. During the epidemic, closely related viruses were isolated from several exotic animals including Himalayan palm civets and raccoon dogs [ 82 ]. Although some human individuals within wet animal markets had serologic evidence of SARS-CoV infection prior to the outbreak, these individuals had no apparent symptoms [ 82 ].
Thus, it is likely that a closely related virus circulated in the wet animal markets for several years before a series of factors facilitated its spread into the larger population. Transmission of SARS-CoV was relatively inefficient, as it only spread through direct contact with infected individuals after the onset of illness. Thus, the outbreak was largely contained within households and healthcare settings [ 86 ], except in a few cases of superspreading events where one individual was able to infect multiple contacts due to an enhanced development of high viral burdens or ability to aerosolize virus.
As a result of the relatively inefficient transmission of SARS-CoV, the outbreak was controllable through the use of quarantining. The virus is capable of entering macrophages and dendritic cells but only leads to an abortive infection [ 87 , 88 ]. Despite this, infection of these cell types may be important in inducing pro-inflammatory cytokines that may contribute to disease [ 89 ]. In fact, many cytokines and chemokines are produced by these cell types and are elevated in the serum of SARS-CoV infected patients [ 90 ].
The exact mechanism of lung injury and cause of severe disease in humans remains undetermined. Viral titers seem to diminish when severe disease develops in both humans and in several animal models of the disease. Furthermore, animals infected with rodent-adapted SARS-CoV strains show similar clinical features to the human disease, including an age-dependent increase in disease severity [ 91 ].
These animals also show increased levels of proinflammatory cytokines and reduced T-cell responses, suggesting a possible immunopathological mechanism of disease [ 92 , 93 ]. However, the outbreak did not accelerate in , although sporadic cases continued throughout the rest of the year.
In April , a spike of over cases and almost 40 deaths occurred, prompting fears that the virus had mutated and was more capable of human-to-human transmission. More likely, the increased number of cases resulted from improved detection and reporting methods combined with a seasonal increase in birthing camels. It is believed that the virus originated from bats, but likely had an intermediate host as humans rarely come in contact with bat secreta.
Serological studies have identified MERS-CoV antibodies in dromedary camels in the Middle East [ 96 ], and cell lines from camels have been found to be permissive for MERS-CoV replication [ 97 ] providing evidence that dromedary camels may be the natural host. More convincing evidence for this comes from recent studies identifying nearly identical MERS-CoVs in both camels and human cases in nearby proximities in Saudi Arabia [ 98 , 99 ]. In one of these studies the human case had direct contact with an infected camel and the virus isolated from this patient was identical to the virus isolated from the camel [ 99 ].
At the present time it remains to be determined how many MERS-CoV cases can be attributed to an intermediate host as opposed to human-to-human transmission. It has also been postulated that human-to-camel spread contributed to the outbreak. Single-stranded RNA viruses however, replicate mainly in the host cell's cytoplasm.
Once a virus infects its host and the viral progeny components are produced by the host's cellular machinery, the assembly of the viral capsid is a non-enzymatic process. It is usually spontaneous. Viruses typically can only infect a limited number of hosts also known as host range. The "lock and key" mechanism is the most common explanation for this range. Certain proteins on the virus particle must fit certain receptor sites on the particular host's cell surface.
The basic process of viral infection and virus replication occurs in 6 main steps. Viruses may infect any type of cell including animal cells , plant cells , and bacterial cells. To view an example of the process of viral infection and virus replication, see Virus Replication: Bacteriophage. You will discover how a bacteriophage , a virus that infects bacteria, replicates after infecting a bacterial cell.
Step 1: Adsorption A bacteriophage binds to the cell wall of a bacterial cell. Step 2: Penetration The bacteriophage injects its genetic material into the bacterium. Step 3: Viral Genome Replication The bacteriophage genome replicates using the bacterium 's cellular components. Step 4: Assembly Bacteriophage components and enzymes are produced and begin to assemble.
Step 5: Maturation Bacteriophage components assemble and phages fully develop. Step 6: Release A bacteriophage enzyme breaks down the bacterial cell wall causing the bacterium to split open. Actively scan device characteristics for identification.
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