Introduction tothe Viruses 23I. OVERVIEW

A virus is an infectious agent that is minimally constructed of two com-ponents: 1) a genome consisting of either ribonucleic acid (RNA) ordeoxyribonucleic acid (DNA), but not both, and 2) a protein-containingstructure (capsid) designed to protect the genome (Figure 23.1A). Manyviruses have additional structural features, for example, an envelopecomposed of a protein-containing lipid bilayer, whose presence orabsence further distinguishes one virus group from another (Figure23.1B). A complete virus particle combining these structural elements iscalled a virion. In functional terms, a virion can be envisioned as a deliv-ery system that surrounds a nucleic acid payload. The delivery systemis designed to protect the genome and enable the virus to bind to hostcells. The payload is the viral genome and may also include enzymesrequired for the initial steps in viral replication—a process that is obli-gately intracellular. The pathogenicity of a virus depends on a greatvariety of structural and functional characteristics. Therefore, evenwithin a closely related group of viruses, different species may producesignificantly distinct clinical pathologies.

II. CHARACTERISTICS USED TO DEFINE VIRUS FAMILIES, GENERA, AND SPECIES

Viruses are divided into related groups, or families, and, sometimes intosubfamilies based on: 1) type and structure of the viral nucleic acid, 2)the strategy used in its replication, 3) type of symmetry of the virus cap-sid (helical versus icosahedral), and 4) presence or absence of a lipidenvelope. Within a virus family, differences in additional specific proper-ties, such as host range, serologic reactions, amino acid sequences of

Figure 23.1General structure: A. non-enveloped; B. enveloped viruses.

Capsid

Capsid

Proteins inenvelopemembrane

Envelope

A

B

Nonenveloped virus

Enveloped virus

Nucleic acid

Nucleic acid

233

UNIT IV:

Viruses

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viral proteins, degree of nucleic acid homology, among others, form thebasis for division into genera (singular, genus) and species (Figure 23.2).Species of the same virus isolated from different geographic locationsmay differ from each other in nucleotide sequence. In this case, they arereferred to as strains of the same species.

A. Genome

The type of nucleic acid found in the virus particle is perhaps themost fundamental and straightforward of viral properties. It may beRNA or DNA, either of which may be single stranded (ss) or doublestranded (ds). The most common forms of viral genomes found innature are ssRNA and dsDNA. However, both dsRNA and ssDNAgenomes are found in viruses of medical significance (Figure 23.3).Single-stranded viral RNA genomes are further subdivided intothose of “positive polarity” (that is, of messenger RNA sense, whichcan, therefore, be used as a template for protein synthesis) andthose of “negative polarity” or are antisense (that is, complementaryto messenger RNA sense, which cannot, therefore, be used directlyas a template for protein synthesis). Viruses containing these twotypes of RNA genomes are commonly referred to as positive-strandand negative-strand RNA viruses, respectively.

B. Capsid symmetry

The protein shell enclosing the genome is, for most virus families,found in either of two geometric configurations (see Figure 23.3):

234 23. Introduction To The Viruses

Figure 23.2Classification of viruses: A. No subfamilies present. B. Subfamiliespresent.

Genus (–virus)For example, Herpesvirus

Subfamily (–virinae)For example, Alphaherpesvirinae

Species For example,

herpes simplex virus

Family (–viridae)For example, Herpesviridae

A B

Figure 23.3Viral families classified according to type of genome, capsid symmetry, and presence or absence of an envelope.RNA is shown in blue, DNA in red, and viral envelope in green. [Note: Numbers indicate chapters where detailed information is presented.]

Single stranded Nonenveloped

Double stranded Nonenveloped

Double stranded Enveloped

Single stranded Positive strand

IcosadedralNonenveloped

Single strandedNegative strand

HelicalEnveloped

Double stranded, Icosahedral

Nonenveloped

Single strandedPositive strandIcosadedral or

helical Enveloped

TYPE OF GENOME

KEY:

PRESENCE OF ENVELOPE

STRANDEDNESS OF GENOME

Single-stranded nucleic acid

Double-stranded nucleic acid

DNA viruses

DNA

RNA viruses

RNA

Enveloped

Nonenveloped

Helical symmetry

Icosahedral symmetry

Parvovirdae (24)

Adenoviridae (24)Papovaviridae (24)

Hepadnaviridae (26)Herpesviridae (25)Poxviridae (25)

Caliciviridae (27)Picornaviridae (27)

Coronaviridae (29)

Flaviviridae (27)Retroviridae (28)Togaviridae (27)

Arenaviridae (29)Bunyaviridae (29)Filoviridae (29)Orthomyxoviridae (29)Paramyxoviridae (29)Rhabdoviridae (29)

Reoviridae (30)

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Figure 23.5Structure of a nonenveloped virus showing icosahedral symmetry.

Capsomer Nucleic acid

Figure 23.4Nucleocapsid of a helical virus.

Capsid

Several rows of protomers havebeen removed to reveal nucleic acidsurrounded by a hollow protein cylinder.

III. Viral Replication: The One-Step Growth Curve 235

Figure 23.6Structure of an enveloped helical virus.

Proteins inenvelopemembrane

Nucleic acid

Capsomer

Envelope

helical (rod shaped or coiled) or icosahedral (spherical or symmet-ric). The capsid is constructed of multiple copies of a singlepolypeptide type (found in helical capsids) or a small number of dif-ferent polypeptides (found in icosahedral capsids), requiring only alimited amount of genetic information to code for these structuralcomponents.

1. Helical symmetry: Capsids with helical symmetry, such as theparamyxoviridae (see p. 312), consist of repeated units of a sin-gle polypeptide species that—in association with the viralnucleic acid—self-assemble into a helical cylinder (Figure 23.4).Each polypeptide unit (protomer) is hydrogen-bonded to neigh-boring protomers. The complex of protomers and nucleic acid iscalled the nucleocapsid. Because the nucleic acid of a virus issurrounded by the capsid, it is protected from environmentaldamage.

2. Icosahedral symmetry: Capsids with icosahedral symmetry aremore complex than those with helical symmetry, in that they con-sist of several different polypeptides grouped into structural sub-assemblies called capsomers. These, in turn, arehydrogen-bonded to each other to form an icosahedron (Figure23.5). The nucleic acid genome is located within the empty spacecreated by the rigid, icosahedral structure.

C. Envelope

An important structural feature used in defining a viral family is thepresence or absence of a lipid-containing membrane surroundingthe nucleocapsid. This membrane is referred to as the envelope. Avirus that is not enveloped is referred to as a naked virus. Inenveloped viruses, the nucleocapsid is flexible and coiled within theenvelope, resulting in most such viruses appearing to be roughlyspherical (Figure 23.6). The envelope is derived from host cell mem-branes. However, the cellular membrane proteins are replaced byvirus-specific proteins, conferring virus-specific antigenicity upon theparticle. Among viruses of medical importance, there are bothnaked and enveloped icosahedral viruses, but all the helical virusesof animals are enveloped and contain RNA.

III. VIRAL REPLICATION: THE ONE-STEP GROWTH CURVE

The one-step growth curve is a representation of the overall change,with time, in the amount of infectious virus in a single cell that has beeninfected by a single virus particle. In practice, this is determined by fol-lowing events in a large population of infected cells in which the infec-tion is proceeding as nearly synchronously as can be achieved bymanipulating the experimental conditions. Whereas the time scale andyield of progeny virus vary greatly among virus families, the basic fea-tures of the infectious cycle are similar for all viruses. The one-stepgrowth curve begins with the eclipse period, which is followed by aperiod of exponential growth (Figure 23.7).

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A. Eclipse period

Following initial attachment of a virus to the host cell, the ability ofthat virus to infect other cells disappears. This is the eclipse period,and it represents the time elapsed from initial entry and disassemblyof the parental virus to the assembly of the first progeny virion.During this period, active synthesis of virus components is occur-ring. The eclipse period for most human viruses falls within a rangeof 1 to 20 hours.

B. Exponential growth

The number of progeny virus produced within the infected cellincreases exponentially for a period of time, then reaches aplateau, after which no additional increase in virus yield occurs.The maximum yield per cell is characteristic for each virus-cell sys-tem and reflects the balance between the rate at which virus com-ponents continue to be synthesized and assembled into virions,and the rate at which the cell loses the synthetic capacity andstructural integrity needed to produce new virus particles. This maybe from 8 to 72 hours or longer, with yields of 100 to 10,000 virionsper cell.

IV. STEPS IN THE REPLICATION CYCLES OF VIRUSES

The individual steps in the virus replication cycle are presented belowin sequence, beginning with virus attachment to the host cell and lead-ing to penetration and uncoating of the viral genome. Gene expressionand replication are followed by assembly and release of viral progeny.

A. Adsorption

The initial attachment of a virus particle to a host cell involves aninteraction between specific molecular structures on the virion sur-face and receptor molecules in the host cell membrane that recog-nize these viral structures (Figure 23.8A).

1. Attachment sites on the viral surface: Some viruses have spe-cialized attachment structures such as the glycoprotein spikesfound in viral envelopes (for example, rhabdoviruses, see p. 310),whereas, for others, the unique folding of the capsid proteinsforms the attachment sites (for example, picornaviruses, seep 284). In both cases, multiple copies of these molecular attach-ment structures are distributed around the surface of the virion.[Note: In some cases, the mechanism by which antibodies neu-tralize viral infectivity is through antibody binding to the viral struc-tures that are required for adsorption (Figure 23.8B).]

2. Host cell receptor molecules: The receptor molecules on the hostcell membrane are specific for each virus family. Not surprisingly,these receptors have been found to be molecular structures thatusually carry out normal cell functions. For example, cellularmembrane receptors for compounds such as growth factors may

Figure 23.7One-step growth curve of a single cellinfected with a single virus particle. Initiation of infection is at zero time.

00

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10

100

1000

10 20Hours

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Exponentialgrowthperiod

Yield percell

236 23. Introduction To The Viruses

Virus

Figure 23.8 A. Attachment of virus to receptor onhost cell membrane. B. Antibodyprevents adsorption of virus.

A

B

Receptor in hostcell membrane

Attached virus

Antibody to viralstructure requiredfor adsorption

Virus fails to bindto host cell receptor

Receptor

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Figure 23.9 Receptor-mediated endocytosis ofvirus particle.

1

2

3 Formation of an endocytotic vesicle

Release of thevirion into cytoplasm

Invagination of the membrane

Binding of a virus

Virion

Host receptor

Endocytotic vesicle 4

IV. Steps in the Replication Cycles of Viruses 237

Figure 23.10Fusion of viral envelope withmembrane of host cell.

Envelopedvirus

Fusion of viralenvelope withthe host cellmembrane

Binding of a virus to ahost cellmembranereceptor

Nucleocapsidenters the cell

1

2

3

also inadvertently serve as receptors for a particular virus. Manyof the compounds that serve as virus receptors are present onlyon specifically differentiated cells or are unique for one animalspecies. Therefore, the presence or absence of host cell recep-tors is one important determinant of tissue specificity within a sus-ceptible host species and also for the susceptibility or resistanceof a species to a given virus. Information about the three-dimen-sional structure of virus-binding sites is being used to designantiviral drugs that specifically interact with these sites, blockingviral adsorption.

B. Penetration

Penetration is the passage of the virion from the surface of the cellacross the cell membrane and into the cytoplasm. There are twoprincipal mechanisms by which viruses enter animal cells: receptor-mediated endocytosis and direct membrane fusion.

1. Receptor-mediated endocytosis: This is basically the same pro-cess by which the cell internalizes compounds, such as growthregulatory molecules and serum lipoproteins, except that theinfecting virus particle is bound to the host cell surface receptorin place of the normal ligand (Figure 23.9). The cell membraneinvaginates, enclosing the virion in an endocytotic vesicle (endo-some). Release of the virion into the cytoplasm occurs by variousroutes, depending on the virus, but, in general, it is facilitated byone or more viral molecules. In the case of an enveloped virus,its membrane may fuse with the membrane of the endosome,resulting in the release of the nucleocapsid into the cytoplasm.Failure to exit the endosome before fusion with a lysosome gen-erally results in degradation of the virion by lysosomal enzymes.Therefore, not all potentially infectious particles are successful inestablishing infection.

2. Membrane fusion: Some enveloped viruses (for example, humanimmunodeficiency virus, see p. 297) enter a host cell by fusion oftheir envelope with the plasma membrane of the cell (Figure23.10). One or more of the glycoproteins in the envelope of theseviruses promotes the fusion. The end result of this process is thatthe nucleocapsid is free in the cytoplasm, whereas the viralmembrane remains associated with the plasma membrane of thehost cell.

C. Uncoating

“Uncoating” refers to the stepwise process of disassembly of thevirion that enables the expression of the viral genes that carry outreplication. For enveloped viruses, the penetration process itself isthe first step in uncoating. In general, most steps of the uncoatingprocess occur within the cell and depend on cellular enzymes.However, in some of the more complex viruses, newly synthesizedviral proteins are required to complete the process. The loss of oneor more structural components of the virion during uncoating pre-

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dictably leads to a loss of the ability of that particle to infect othercells, which is the basis for the eclipse period of the growth curve(see Figure 23.7). It is during this phase in the replication cycle thatviral gene expression begins.

D. Mechanisms of DNA virus genome replication

Each virus family differs in significant ways from all others in termsof the details of the macromolecular events comprising the replica-tion cycle. The wide range of viral genome sizes gives rise to greatdifferences in the number of proteins for which the virus can code. Ingeneral, the smaller the viral genome, the more the virus mustdepend on the host cell to provide the functions needed for viralreplication. For example, some small DNA viruses, such asPolyomaviruses (see p. 249), produce only one or two replication-related gene products, which function to divert host cell processesto those of viral replication. Other larger DNA viruses, such aspoxviruses (see p. 270), provide virtually all enzymatic and regula-tory molecules needed for a complete replication cycle. Most DNA

238 23. Introduction To The Viruses

Figure 23.11Replication of DNA viruses.

Parental DNA

Transcription of early genes(fraction of the viral genometranscribed prior to initiation of viral DNA synthesis)

Transcription of late genes(fraction of the viral genometranscribed after initiation of viral DNA synthesis)

Early mRNAsSynthesis of early proteins

Synthesis of late proteins

TranslationEarly proteins

Early proteins( + cell enzymes)

Replication ofvirus DNA

Progeny DNA

Assembly ofnucleocapids

Late mRNAs

TranslationLate proteins

1

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3

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IV. Steps in the Replication Cycles Of Viruses 239

(+) ssRNA

(–) ssRNA

Translation Cleavage

Proteins includeRNA-dependant RNA polymerase

Assembly into nucleocapsid

Viral proteins

More viral proteins

Polyprotein

(+) ssRNA

(+) ssRNA serves as the template for complementary (–) strand synthesis

Figure 23.12Type I virus with a ssRNA genomeof (+) polarity replicates via a complementary (–) strand intermediate.

RNA-dependant RNA polymerase

1

2

(–) ssRNA serves as the template for complementary (+) strand synthesis

3

ssRNA serves as mRNA

viruses assemble in the nucleus, whereas most RNA virusesdevelop solely in the cytoplasm. Figure 23.11 outlines the essentialfeatures of gene expression and replication of DNA viruses.

E. Mechanisms of RNA virus genome replication

Viruses with RNA genomes must overcome two specific problemsthat arise from the need to replicate the viral genome and to pro-duce a number of viral proteins in eukaryotic host cells. First, thereis no host cell RNA polymerase that can use the viral parental RNAas a template for synthesis of complementary RNA strands. Second,translation of eukaryotic mRNAs begins at only a single initiationsite, and they are, therefore, translated into only a single polypep-tide. However, RNA viruses, which frequently contain only a singlemolecule of RNA, must express the genetic information for at leasttwo proteins: an RNA-dependent RNA polymerase and a minimumof one type of capsid protein. Although the replication of each RNAvirus family has unique features, the mechanisms evolved to sur-mount these restrictions can be grouped into four broad patterns (or“types”) of replication.

1. Type I—RNA viruses with a single-stranded genome (ssRNA) of(+) polarity that replicates via a complementary (–) strand inter-mediate: In Type I viral replication, the infecting parental RNAmolecule serves both as mRNA and, later, as a template for syn-thesis of the complementary (–) strand (Figure 23.12).

a. Role of (+) ssRNA as mRNA: Because the parental RNAgenome is of (+), or messenger, polarity, it can be translateddirectly upon uncoating and associating with cellular ribo-somes. The product is usually a single polyprotein from whichindividual polypeptides, such as RNA-dependent RNA poly-merase and various proteins of the virion, are cleaved by aseries of proteolytic processing events carried out by a pro-tease domain of the polyprotein (see Figure 23.12).

b. Role of (+) ssRNA as the template for complementary (–)strand synthesis: The viral (+) ssRNA functions early in infec-tion, not only as mRNA for translation of polyproteins but alsoas a template for virus-encoded RNA-dependent RNA poly-merase to synthesize complementary (–) ssRNA (see Figure23.12). The progeny (–) strands, in turn, serve as templates forsynthesis of progeny (+) strands, which can serve as additionalmRNAs, amplifying the capacity to produce virion proteins forprogeny virus. When a sufficient quantity of capsid proteins hasaccumulated later in the infection, progeny (+) ssRNAs begin tobe assembled into newly formed nucleocapsids.

2. Type II—viruses with a ssRNA genome of (–) polarity that repli-cate via a complementary (+) strand intermediate: Viral genomeswith (–) polarity, similar to the (+) strand genomes, also have twofunctions: 1) to provide information for protein synthesis and 2) toserve as templates for replication. Unlike (+) strand genomes,

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however, the (–) strand genomes cannot accomplish these goalswithout prior construction of a complementary (+) strand interme-diate (Figure 23.13).

a. Mechanism of replication of viral ssRNA with (–) polarity:The replication problems for these viruses are twofold. First,the (–) strand genome cannot be translated, and, therefore,the required viral RNA polymerase cannot be synthesizedimmediately following infection. Second, the host cell has noenzyme capable of transcribing the (–) strand RNA genomeinto (+) strand RNAs capable of being translated. The solutionto these problems is for the infecting virus particle to containviral RNA-dependent RNA polymerase and to bring thisenzyme into the host cell along with the viral genome. As aconsequence, the first synthetic event after infection is gener-ation of (+) strand mRNAs from the parental viral (–) strandRNA template.

b. Mechanisms for multiple viral protein synthesis in Type IIviruses: The synthesis of multiple proteins is achieved in oneof two ways among the (–) strand virus families: 1) The viralgenome may be transcribed into a number of individualmRNAs, each specifying a single, polypeptide. 2) Alternatively,the (–) strand viral genome may be segmented (that is, com-posed of a number of different RNA molecules, most of whichcode for a single polypeptide).

c. Production of infectious virus particles: Although the detailsdiffer, the flow of information in both segmented and unseg-mented genome viruses is basically the same. In the Type IIreplication scheme, an important control point is the shift fromsynthesis of (+) strand mRNA to progeny (–) strand RNAmolecules that can be packaged in the virions. This shift is nota result of activity of a different polymerase, but rather a resultof interaction of (+) strand RNA molecules with one or morenewly synthesized proteins. This enhances the availability ofthe (+) strands as templates for the synthesis of genomic (–)strands.

3. Type III—viruses with a dsRNA genome: The dsRNA genome issegmented, with each segment coding for one polypeptide(Figure 23.14). However, eukaryotic cells do not have an enzymecapable of transcribing dsRNA. Type III viral mRNA transcriptsare, therefore, produced by virus-coded, RNA-dependent RNApolymerase (transcriptase) located in a subviral core particle.This particle consists of the dsRNA genome and associatedvirion proteins, including the transcriptase. The mechanism ofreplication of the dsRNA is unique, in that the (+) RNA transcriptsare not only used for translation but also as templates for com-plementary (–) strand synthesis, resulting in the formation ofdsRNA progeny.

240 23. Introduction To The Viruses

(+) ssRNA mRNAs

Assembly into nucleocapsids

(–) ssRNA

(–) ssRNA

Figure 23.13Type II virus with an ssRNA genomeof (–) polarity that replicates via a complementary (+) strand inter-mediate.

RNA-dependent RNA polymerasefrom infecting virus particle

Viral proteins

1

RNA-dependent RNA polymerase

(+) ssRNA serves as a template for complementary (–) strand (viralgenome) synthesis-

2

Transcription of (+) strand mRNAs from the parental viral (–) strand RNA template

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4. Type IV—viruses with a genome of ssRNA of (+) polarity that isreplicated via a DNA intermediate: The conversion of a (+) strandRNA to a double-stranded DNA is accomplished by an RNA-dependent DNA polymerase, commonly referred to as a “reversetranscriptase,” that is contained in the virion. The resulting dsDNAbecomes integrated into the cell genome by the action of a viral“integrase.” Viral mRNAs and progeny (+) strand RNA genomesare transcribed from this integrated DNA by the host cell RNApolymerase (Figure 23.15).

F. Assembly and release of progeny viruses

Assembly of nucleocapsids generally takes place in the host cellcompartment where the viral nucleic acid replication occurs (thatis, in the cytoplasm for most RNA viruses and in the nucleus formost DNA viruses). For DNA viruses, this requires that capsidproteins be transported from their site of synthesis (cytoplasm) tothe nucleus. The various capsid components begin to self-assem-ble, eventually associating with the nucleic acid to complete thenucleocapsid.

1. Naked viruses: In naked (unenveloped) viruses, the virion is com-plete at this point. Release of progeny is usually a passive eventresulting from the disintegration of the dying cell and, therefore,may be at a relatively late time after infection.

2. Enveloped viruses: In enveloped viruses, virus-specific glycopro-teins are synthesized and transported to the host cell membrane

Assembly into nucleocapsids

dsRNA (segmented)

Figure 23.14Type III virus with a dsRNA genome.

RNA-dependent RNA polymerase

RNA-dependent RNA polymerasefrom infectingvirus particle

mRNAs Viral proteins

1 Transcription of (+) strand RNA from virus dsRNA template

(+) RNA strands serve both as mRNA and template for complementary (–) RNA strand synthesis

2

IV. Steps in the Replication Cycles Of Viruses 241

Viral RNA-dependent DNA polymerase(reverse transcriptase)

Host RNApolymerase

Host RNApolymerase

Integration into host DNAby viral integrase

(+) ssRNA

RNADNA

DNADNA

Figure 23.15Type IV virus with a ssRNA genome of (+) polarity that replicates via a DNA intermediate.

Viral RNA-dependent DNA polymerase(reverse transcriptase)

Viral mRNAs

Translation

Viral proteins

Assembly into nucleocapsid

Viral (+) ssRNA

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242 23. Introduction To The Viruses

Figure 23.16Release of enveloped virus from a host cell by the process of “budding.”

Viral protein

Host cell membrane

The enveloped virion is released from the host cell.

Virus-specific glycoproteins are synthesized and transported to the host cell membrane.

A nucleocapsid is enveloped bythe host cell membrane.

1

5

The host cell membrane provides the viral envelope by a process of "budding."

4

3

The cytoplasmic domains of membrane proteins bindnucleocapsids.

2

Nucleocapsid

INFOLINK

1See Chapter 14 in Lippincott’s Illustrated Reviews: Biochemistry for a discussion of the mechanism of insertion of glycoproteins into cell membranes.

in the same manner as cellular membrane proteins.1 Wheninserted into the membrane, they displace the cellular glycopro-teins, resulting in patches on the cell surface that have viral anti-genic specificity. The cytoplasmic domains of these proteinsassociate specifically with one or more additional viral proteins(matrix proteins) to which the nucleocapsids bind. Final matura-tion then involves envelopment of the nucleocapsid by a processof “budding” (Figure 23.16). A consequence of this mechanism ofviral replication is that progeny virus are released continuouslywhile replication is proceeding within the cell and ends when thecell loses its ability to maintain the integrity of the plasma mem-brane. A second consequence is that, with most envelopedviruses, all infectious progeny are extracellular. The exceptionsare those viruses that acquire their envelopes by budding throughinternal cell membranes such as those of the endoplasmic reticu-lum or nucleus. Viruses containing lipid envelopes are sensitiveto damage by harsh environments and, therefore, tend to betransmitted by the respiratory, parenteral, and sexual routes.Nonenveloped viruses are more stable to hostile environmentalconditions and often transmitted by the fecal–oral route.

G. Effects of viral infection on the host cell

The response of a host cell to infection by a virus ranges from: 1) lit-tle or no detectable effect; to 2) alteration of the antigenic specificityof the cell surface due to presence of virus glycoproteins; to 3) latentinfections that, in some cases, cause cell transformation; or, ulti-mately, to 4) cell death due to expression of viral genes that shut offessential host cell functions (Figure 23.17).

1. Viral infections in which no progeny virus are produced: In thiscase, the infection is referred to as abortive. An abortive responseto infection is commonly caused by: 1) a normal virus infectingcells that are lacking in enzymes, promoters, transcription factors,or other compounds required for complete viral replication, inwhich case the cells are referred to as nonpermissive; 2) infectionby a defective virus of a cell that normally supports viral replica-tion (that is, by a virus that itself has genetically lost the ability toreplicate in that cell type); or 3) death of the cell as a conse-quence of the infection, before viral replication has been com-pleted.

2. Viral infections in which the host cell may be altered antigeni-cally but is not killed, although progeny virus are released: Inthis case, the host cell is permissive, and the infection is produc-tive (progeny virus are released from the cell), but viral replicationand release neither kills the host cell nor interferes with its abilityto multiply and carry out differentiated functions. The infection is,

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IV. Steps in the Replication Cycles Of Viruses 243

Figure 23.17Effects of viral infection on a host cell.

Abortive viral infections in whichno progeny virus are produced.Abortive viral infections in whichno progeny virus are produced.

Host cell Host cell

Virion

Viral infections that result in a latent viral state in the host cell.Viral infections that result in a latent viral state in the host cell.

1

Viral infections resulting in host cell death and production of progeny.

Viral infections resulting in host cell death and production of progeny.

4

3

Productive viral infections in which the host cell is not killed, although progeny virus are released.

Productive viral infections in which the host cell is not killed, although progeny virus are released.

2

Some viral infections result in the persistence of the viral genome inside a host cell with no production of progeny virus. The viral nucleic acid may or may not be integrated into the host chromosome, depending on the virus.

Some viral infections result in the persistence of the viral genome inside a host cell with no production of progeny virus. The viral nucleic acid may or may not be integrated into the host chromosome, depending on the virus.

Such latent viruses can be reactivated months or yearsin the future, leading to aproductive infection.

Such latent viruses can be reactivated months or yearsin the future, leading to aproductive infection.

therefore, said to be persistent. The antigenic specificity of the cellsurface may be altered as a result of the insertion of viral glyco-proteins.

3. Viral infections that result in a latent viral state in the host cell:Some viral infections result in the persistence of the viral genomeinside a host cell with no production of progeny virus. Such latentviruses can be reactivated months or years in the future, leadingto a productive infection. Some latently infected cells contain viralgenomes that are stably integrated into a host cell chromosome.This can cause alterations in the host cell surface; cellularmetabolic functions; and, significantly, cell growth and replicationpatterns. Such viruses may induce tumors in animals, in whichcase they are said to be tumor viruses, and the cells they infectare transformed.

4. Viral infections resulting in host cell death and production ofprogeny virus: Eliminating host cell competition for syntheticenzymes and precursor molecules increases the efficiency withwhich virus constituents can be synthesized. Therefore, the typi-cal result of a productive (progeny-yielding) infection by a cytoci-dal virus is the shutoff of much of the cell’s macromolecularsyntheses by one or more of the virus gene products, causing thedeath of the cell. Such an infection is said to be lytic. The mecha-nism of the shutoff varies among the viral families.

In summary, all viruses:

• are small;

• contain only one species of nucleic acid, either DNA orRNA;

• attach to their host cell with a specific receptor-bindingprotein; and

• express the information contained in the viral genome(DNA or RNA) using the cellular machinery of the hostcell

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