H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003) (796244), страница 58
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The viral proteinsare then transported back into the nucleus, where some ofthem either replicate the viral DNA directly or direct cellular proteins to replicate the viral DNA, as in the case of SV40discussed in the last section. Assembly of the capsid proteinswith the newly replicated viral DNA occurs in the nucleus,yielding hundreds to thousands of progeny virions.Most plant and animal viruses with an RNA genome donot require nuclear functions for lytic replication. In some140CHAPTER 4 • Basic Molecular Genetic Mechanisms FIGURE 4-40 Lytic replicationLysis/releasecycle of E.
coli bacteriophage T4, anonenveloped virus with a doublestranded DNA genome. After viral coatproteins at the tip of the tail in T4interact with specific receptor proteinson the exterior of the host cell, the viralgenome is injected into the host (step 1 ).Host-cell enzymes then transcribeviral “early” genes into mRNAs andsubsequently translate these into viral“early” proteins (step 2 ). The earlyproteins replicate the viral DNA andinduce expression of viral “late” proteinsby host-cell enzymes (step 3 ). The virallate proteins include capsid and assembly proteins and enzymes that degradethe host-cell DNA, supplying nucleotidesfor synthesis of more viral DNA.
Progenyvirions are assembled in the cell (step 4 )and released (step 5 ) when viral proteinslyse the cell. Newly liberated virusesinitiate another cycle of infection in otherhost cells.Adsorption/injection5E. colichromosome1Free virionT4 DNAExpression2 of viral earlyproteinsAssembly 4Viralproteins3Replication of viral DNAExpression of viral late proteinsRabies virusNucleocapsid proteinLipid bilayerMatrix proteinGenomic RNAReceptor-binding glycoproteinViral RNA polymerase1 AdsorptionBudding 13Virus receptorFusion 912Associationat membraneCytosol2 Endocytosis11GolgiProgeny capsidassemblyEndosomeTransport 8Matrix andnucleocapsid 10synthesis3 FusionViralmRNA7GlycoproteinsynthesisERNucleus5 Replication6TranscriptionCell membrane4Release4.7 • Viruses: Parasites of the Cellular Genetic Systemof these viruses, a virus-encoded enzyme that enters the hostduring penetration transcribes the genomic RNA intomRNAs in the cell cytoplasm.
The mRNA is directly translated into viral proteins by the host-cell translation machinery. One or more of these proteins then produces additionalcopies of the viral RNA genome. Finally, progeny genomesare assembled with newly synthesized capsid proteins intoprogeny virions in the cytoplasm.After the synthesis of hundreds to thousands of new virions has been completed, most infected bacterial cells andsome infected plant and animal cells are lysed, releasing allthe virions at once. In many plant and animal viral infections, however, no discrete lytic event occurs; rather, the deadhost cell releases the virions as it gradually disintegrates.As noted previously, enveloped animal viruses are surrounded by an outer phospholipid layer derived from theplasma membrane of host cells and containing abundantviral glycoproteins.
The processes of adsorption and releaseof enveloped viruses differ substantially from these processesin nonenveloped viruses. To illustrate lytic replication ofenveloped viruses, we consider the rabies virus, whose nucleocapsid consists of a single-stranded RNA genome surrounded by multiple copies of nucleocapsid protein. Like FIGURE 4-41 Lytic replication cycle of rabies virus, anenveloped virus with a single-stranded RNA genome.
Thestructural components of this virus are depicted at the top. Notethat the nucleocapsid is helical rather than icosahedral. After avirion adsorbs to multiple copies of a specific host membraneprotein (step 1 ), the cell engulfs it in an endosome (step 2 ).A cellular protein in the endosome membrane pumps H ionsfrom the cytosol into the endosome interior. The resultingdecrease in endosomal pH induces a conformational change inthe viral glycoprotein, leading to fusion of the viral envelopewith the endosomal lipid bilayer membrane and release of thenucleocapsid into the cytosol (steps 3 and 4 ). Viral RNApolymerase uses ribonucleoside triphosphates in the cytosol toreplicate the viral RNA genome (step 5 ) and to synthesize viralmRNAs (step 6 ).
One of the viral mRNAs encodes the viraltransmembrane glycoprotein, which is inserted into themembrane of the endoplasmic reticulum (ER) as it is synthesizedon ER-bound ribosomes (step 7 ). Carbohydrate is added to thelarge folded domain inside the ER lumen and is modified as themembrane and the associated glycoprotein pass through theGolgi apparatus (step 8 ). Vesicles with mature glycoprotein fusewith the host plasma membrane, depositing viral glycoproteinon the cell surface with the large receptor-binding domain outside the cell (step 9 ).
Meanwhile, other viral mRNAs are translated on host-cell ribosomes into nucleocapsid protein, matrixprotein, and viral RNA polymerase (step 10 ). These proteins areassembled with replicated viral genomic RNA (bright red) intoprogeny nucleocapsids (step 11), which then associate with thecytosolic domain of viral transmembrane glycoproteins in theplasma membrane (step 12). The plasma membrane is foldedaround the nucleocapsid, forming a “bud” that eventually isreleased (step 13).141▲ EXPERIMENTAL FIGURE 4-42 Progeny virions ofenveloped viruses are released by budding from infectedcells. In this transmission electron micrograph of a cell infectedwith measles virus, virion buds are clearly visible protruding fromthe cell surface.
Measles virus is an enveloped RNA virus with ahelical nucleocapsid, like rabies virus, and replicates as illustratedin Figure 4-41. [From A. Levine, 1991, Viruses, Scientific AmericanLibrary, p. 22.]other lytic RNA viruses, rabies virions are replicated in thecytoplasm and do not require host-cell nuclear enzymes. Asshown in Figure 4-41, a rabies virion is adsorbed by endocytosis, and release of progeny virions occurs by buddingfrom the host-cell plasma membrane. Budding virionsare clearly visible in electron micrographs of infected cells, asillustrated in Figure 4-42. Many tens of thousands of progeny virions bud from an infected host cell before it dies.Viral DNA Is Integrated into the Host-CellGenome in Some Nonlytic Viral Growth CyclesSome bacterial viruses, called temperate phages, can establisha nonlytic association with their host cells that does not killthe cell. For example, when bacteriophage infects E.
coli,the viral DNA may be integrated into the host-cell chromosome rather than being replicated. The integrated viral DNA,called a prophage, is replicated as part of the cell’s DNAfrom one host-cell generation to the next. This phenomenonis referred to as lysogeny. Under certain conditions, theprophage DNA is activated, leading to its excision from thehost-cell chromosome, entrance into the lytic cycle, and subsequent production and release of progeny virions.142CHAPTER 4 • Basic Molecular Genetic MechanismsGenomicssRNARetrovirusproteinsReversetranscriptase51FusionBuddingHost-cellchromosomal DNANucleocapsidReversetranscriptionOverview Animation: Life Cycle of a RetrovirusMEDIA CONNECTIONS4 Transcription2ProvirusTransport tonucleus andintegration3▲ FIGURE 4-43 Retroviral life cycle.
Retroviruses havea genome of two identical copies of single-stranded RNAand an outer envelope. Step 1 : After viral glycoproteins inthe envelope interact with a specific host-cell membraneprotein, the retroviral envelope fuses directly with theplasma membrane, allowing entry of the nucleocapsidinto the cytoplasm of the cell. Step 2 : Viral reversetranscriptase and other proteins copy the viral ssRNAgenome into a double-stranded DNA. Step 3 : The viralThe genomes of a number of animal viruses also can integrate into the host-cell genome. Probably the most important are the retroviruses, which are enveloped viruses with agenome consisting of two identical strands of RNA. Theseviruses are known as retroviruses because their RNA genomeacts as a template for formation of a DNA molecule—theopposite flow of genetic information compared with themore common transcription of DNA into RNA.
In the retroviral life cycle (Figure 4-43), a viral enzyme called reversetranscriptase initially copies the viral RNA genome into singlestranded DNA complementary to the virion RNA; the sameenzyme then catalyzes synthesis of a complementary DNAstrand. (This complex reaction is detailed in Chapter 10when we consider closely related intracellular parasites calledretrotransposons.) The resulting double-stranded DNA is integrated into the chromosomal DNA of the infected cell. Finally, the integrated DNA, called a provirus, is transcribedby the cell’s own machinery into RNA, which either is translated into viral proteins or is packaged within virion coatproteins to form progeny virions that are released by budding from the host-cell membrane. Because most retrovirusesdo not kill their host cells, infected cells can replicate, pro-Viral DNAdsDNA is transported into the nucleus and integrated into oneof many possible sites in the host-cell chromosomal DNA.
Forsimplicity, only one host-cell chromosome is depicted. Step 4 :The integrated viral DNA (provirus) is transcribed by the host-cellRNA polymerase, generating mRNAs (dark red) and genomicRNA molecules (bright red). The host-cell machinery translatesthe viral mRNAs into glycoproteins and nucleocapsid proteins.Step 5 : Progeny virions then assemble and are released bybudding as illustrated in Figure 4-41.ducing daughter cells with integrated proviral DNA. Thesedaughter cells continue to transcribe the proviral DNA andbud progeny virions.Some retroviruses contain cancer-causing genes(oncogenes), and cells infected by such retrovirusesare oncogenically transformed into tumor cells.Studies of oncogenic retroviruses (mostly viruses of birds andmice) have revealed a great deal about the processes thatlead to transformation of a normal cell into a cancer cell(Chapter 23).Among the known human retroviruses are human T-celllymphotrophic virus (HTLV), which causes a form ofleukemia, and human immunodeficiency virus (HIV), whichcauses acquired immune deficiency syndrome (AIDS).
Bothof these viruses can infect only specific cell types, primarilycertain cells of the immune system and, in the case of HIV,some central nervous system neurons and glial cells. Onlythese cells have cell-surface receptors that interact with viralenvelope proteins, accounting for the host-cell specificity ofthese viruses. Unlike most other retroviruses, HIV eventuallykills its host cells. The eventual death of large numbers ofPerspectives for the Futureimmune-system cells results in the defective immune response characteristic of AIDS.Some DNA viruses also can integrate into a host-cellchromosome.
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