VIRUS

Viruses Differ from Bacteria

• Much smaller
• Lack the enzymes necessary for synthesis of protein and nucleic acid
• Do not have cellular organization or ribosomes
• Do not divide by binary fission or grow in inanimate objects/media
• Possess either RNA or DNA
• Resistance to antibiotic

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Virus�(Latin meaning toxin or poison)

• argued whether viruses are living organisms.
• some consider them non-living as they do not meet the criteria of the definition of life. e.g. unlike most organisms, viruses do not have cells.
• however, viruses have genes and evolve by natural selection.
• described as organisms at the edge of life.

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Virus�(Latin meaning toxin or poison)

• sub-microscopic infectious agent
• unable to grow or reproduce outside a host cell.
• Each viral particle, or virion, consists of genetic material, DNA or RNA, within a protective protein coat called a capsid.

Virus�(Latin meaning toxin or poison)

• Viral infections in human as well as animal hosts, usually result in an immune response and disease.
• Antibiotics have no effect on viruses, but antiviral drugs have been developed to treat life-threatening infections.
• Vaccines that produce lifelong immunity can prevent virus infections.

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Shape varies from simple helical and icosahedral (polyhedral or near-spherical) forms, to more complex structures with tails or an envelope.

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Morphology

Pox virus

• infect cellular forms of life and
• grouped into

animal,

plant and

bacterial viruses.

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Capsid

• Protein shell that encloses the nucleic acid; with its enclosed nucleic acid, it is called the nucleocapsid.

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• Composed of protein organized in subunits known as capsomers.

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• They are closely associated with the nucleic acid and reflect its configuration, either a rod-shaped helix or a polygon-shaped sphere.

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Capsid

The capsid has three functions:

1) it protects the nucleic acid from digestion by enzymes,

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2) contains special sites on its surface that allow the virion to attach to a host cell, and

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3) provides proteins that enable the virion to penetrate the host cell membrane and, in some cases, to inject the infectious nucleic acid into the cell's cytoplasm.

Under the right conditions, viral RNA in a liquid suspension of protein molecules will self-assemble a capsid to become a functional and infectious virus.

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Envelope (glycoprotein envelope surrounding the nucleocapsid)

• Composed of two lipid layers interspersed with protein molecules (lipoprotein bilayer) and may contain material from the membrane of a host cell as well as that of viral origin.

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• Many viruses also develop spikes made of glycoprotein on their envelopes that help them to attach to specific cell surfaces.

Morphology

Nucleic Acid

• Nucleic acid of each virus encodes the genetic information for the synthesis of all proteins.

• Most viruses maintain all their genetic information with the single-stranded RNA.

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There are two types of RNA-based viruses.

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• In most, the genomic RNA is termed a plus strand because it acts as messenger RNA for direct synthesis (translation) of viral protein.

• A few, however, have negative strands of RNA.

Icosahedral

Virus classification

• involves naming and placing viruses into a taxonomic system.
• due to the pseudo-living nature of viruses, which are not yet definitively living or non-living.
• virus classification is the subject of ongoing debate and proposals
• do not fit neatly into the established biological classification system in place for cellular organisms, such as plants and animals, for several reasons.

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Virus classification

• is based mainly on phenotypic chracteristics, including

* morphology

* nucleic acid type,

* mode of replication,

* host organisms, and

* the type of disease they cause

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Viruses Classification

A combination of two main schemes is currently in widespread use for the classification of viruses.

1. David Baltimore, a Nobel Prize-winning biologist, devised the Baltimore classification system, which places viruses into one of seven groups.

These groups are designated by Roman numerals and separate viruses based on their mode of replication, and genome type

2. International Committee on Taxonomy of Viruses: (accompanying Baltimore classification)

1 Classification systems

• 1.1 Baltimore classification
• 1.2 ICTV classification

2 Virus classification

• 2.1 DNA viruses
• 2.2 RNA viruses
• 2.3 Reverse transcribing viruses

3 Subviral agents

• 3.1 Viroids
• 3.2 Satellites

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Baltimore classification

• places viruses into one of seven groups depending on a combination of their nucleic acid (DNA or RNA), strandedness (single-stranded or double-stranded), and method of replication.

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• Other classifications are determined by

the disease caused by the virus or

its morphology,

neither of which are satisfactory due to

different viruses either causing the same disease or

looking very similar.

In addition, viral structures are often difficult to determine under the microscope.

Viruses can be placed in one of the seven following groups:

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Baltimore classification

• Group I: double-stranded (ds) DNA viruses
• Group II: single-stranded (ss) DNA viruses

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• Group III: ds RNA viruses
• Group IV: positive-sense ss RNA viruses
• Group V: negative-sense ss RNA viruses

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• Group VI: reverse transcribing RNA viruses
• Group VII: reverse transcribing DNA viruses

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DNA virus

• A DNA virus is a virus that has DNA as its genetic material and replicates using a DNA-dependent DNA polymerase.

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• The nucleic acid is usually double-stranded DNA (dsDNA) but may also be single-stranded DNA (ssDNA). DNA viruses belong to either Group I or Group II of the Baltimore classification system for viruses.

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• Single-stranded DNA is usually expanded to double-stranded in infected cells.

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• Although Group VII viruses such as hepatitis B contain a DNA genome, they are not considered DNA viruses according to the Baltimore classification, but rather reverse transcribing viruses because they replicate through an RNA intermediate.

DNA viruses

• Group I: viruses possess double-stranded DNA and include such virus families as Herpesviridae (herpes viruses), Poxviridae (chickenpox and smallpox) and many tailed bacteriophages. The mimivirus was also placed into this group.

• Group II: viruses possess single-stranded DNA and include such virus families as Parvoviridae and the important bacteriophage M13

RNA virus

• An RNA virus is a virus that has ribonucleic acid (RNA) as its genetic material and does not replicate using a DNA intermediate.

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• RNA viruses belong to either Group III, Group IV or Group V of the Baltimore classification system of classifying viruses.

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• Their nucleic acid is usually single-stranded RNA (ssRNA) but may be double-stranded RNA (dsRNA).

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• Notable human pathogenic RNA viruses include SARS, Influenza and Hepatitis C viruses.

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Single-stranded RNA viruses and RNA Sense

• RNA viruses can be further classified according to the sense or polarity of their RNA into negative-sense and positive-sense RNA viruses.

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• Positive-sense viral RNA is identical to viral mRNA and thus can be immediately translated by the host cell.

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• Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation.

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• As such, purified RNA of a positive-sense virus can directly cause infection though it may be less infectious than the whole virus particle.

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• Purified RNA of a negative-sense virus is not infectious by itself as it needs to be transcribed into positive-sense RNA.

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Double-stranded RNA viruses

• The double-stranded (ds)RNA viruses represent a diverse group of viruses that vary widely in host range (humans, animals, plants, fungi, and bacteria), genome segment number (one to twelve), and virion organization

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• Members of this group include the rotaviruses, renowned globally as the commonest cause of gastroenteritis in young children, and bluetongue virus, an economically important pathogen of cattle and sheep.

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RNA viruses

• Group III: viruses possess double-stranded RNA genomes. These genomes are always segmented.

• Group IV: viruses possess positive-sense single-stranded RNA genomes. Many well known viruses are found in this group, including the SARS virus, hepatitis C virus, yellow fever virus, and rubella virus.

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• Group V: viruses possess negative-sense single-stranded RNA genomes. The deadly Ebola and Marburg viruses are well known members of this group, along with measles, mumps and rabies.

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Reverse Transcribing Viruses

• Replicate using reverse transcription, which is the formation of DNA from an RNA template.

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• Viruses containing RNA genomes use a DNA intermediate to replicate, whereas those containing DNA genomes use an RNA intermediate during genome replication.

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• Both types use the reverse transcriptase enzyme to carry out the nucleic acid conversion.

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• Both types are susceptible to antiviral drugs that inhibit the reverse transcriptase enzyme, e.g. zidovudine and lamivudine.

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Reverse Transcribing Viruses

• Group VI: viruses possess single-stranded RNA genomes and replicate using reverse transcriptase. The retroviruses are included in this group, of which HIV is a member.

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• Group VII: viruses possess double-stranded DNA genomes and replicate using reverse transcriptase. The hepatitis B virus can be found in this group.

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ICTV classification

• The International Committee on Taxonomy of Viruses devised and implemented several rules on the naming and classification of viruses early in the 1990's.

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• Viral classification starts at the level of order and suffixes given in italics:

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ICTV classification

• Order (-virales)
• Family (-viridae)
• Subfamily (-virinae)
• Genus (-virus)
• Species (-virus)

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Approximately 80 families and 4000 species of virus are known.

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Subviral agents�The following agents are smaller than viruses but have some of their properties.

• Viroids
• Family Pospiviroidae
• Genus Pospiviroid; type species: Potato spindle tuber viroid
• Genus Hostuviroid; type species: Hop stunt viroid
• Genus Cocadviroid; type species: Coconut cadang-cadang viroid
• Genus Apscaviroid; type species: Apple scar skin viroid
• Genus Coleviroid; type species: Coleus blumei viroid 1
• Family Avsunviroidae
• Genus Avsunviroid; type species: Avocado sunblotch viroid
• Genus Pelamoviroid; type species: Peach latent mosaic viroid

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Subviral Entities

VIROIDS (Virus like but not)

• Infectious agents composed exclusively of a single piece of circular single stranded RNA that has some double-stranded regions.  

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• Because of their simplified structures both prions and viroids are sometimes called subviral particles.

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• Viroids mainly cause plant diseases but have recently been reported to cause a human disease

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Comparison of Viroid and RNA Virus Structures

RNA Viruses Viroids

• 1. RNA enclosed in capsid RNA naked

• 2. RNA size 1.2x10(6) to 1.2x10(7) daltons RNA size1.1-1.3x10(5) daltons

• 3. May have modified nucleotides Only the standard four nucleotides
• 4. Genome may be segmented Only a single molecule of RNA
• 5. Linear RNA molecules that may be ds Circular RNA molecule that is self-complementary
• 6. Exonuclease sensitive Exonuclease resistant

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• Viroid has 5 domains in nucleotide sequence. T1(LH), P, C, V and T2(RH)

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• C= Conserved (most common), P= Pathogenic, V= Variable, and T1 & T2 = Left and right termini.

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• In C domain one or more inverted repeat sequences of 9 to 10 bases length plays and important role in viroid function.

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What proteins do viroids encode?

•  Viroid does not contain much genetic information

• Viruses can encode a surprising number of proteins with a strategy for reusing the same bases where as viroids do not encode any proteins at all.

• Cell fraction schemes indicates that ~ viroids reproduce in the nucleolus, but search for viroids specific proteins in the nucleoplasm and cytoplasm of infected cells

• Viroids must be able to reproduce themselves and cause their characteristic diseases in their plant host using only host cell proteins

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What host enzymes do viroids use to replicate themselves?

• Most ss RNA viruses replicate by creating an intermediate that is complementary to genome to serve as the template

• - Viroids may make use of the host cell enzyme RNA polymerase II that is responsible for transcription of host mRNAs.

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What other subviral entities have been found?

• In plants

-          Satellite viruses

-          Sattelite RNAs

• Animal
• - Hepatitis delta virus (HDV)

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Satellites

• Satellite viruses
• Single-stranded RNA satellite viruses
• Subgroup 1: Chronic bee-paralysis satellite virus
• Subgroup 2: Tobacco necrosis satellite virus

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• Satellite nucleic acids
• Single-stranded satellite DNAs
• Double-stranded satellite RNAs
• Single-stranded satellite RNAs
• Subgroup 1: Large satellite RNAs
• Subgroup 2: Small linear satellite RNAs
• Subgroup 3: Circular satellite RNAs

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Origin of Subviral Entities

•  Subviral entities can be fitted in to various schemes proposed for viruses

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- Satellite viruses follow degeneration pathway

- Many of satellite RNAs may have arisen from satellite viruses as that degenerative process

- Viroids are derived from cellular RNA molecules which are self replicating.

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Difference between Viroids & subviral entity

• Viroids are capable of autonomous replication but subviral entity needs helper virus that provides some essential function in their replication and transmission cycle.

• High degree of specificity in each satellite/helper virus relationship

• No significant sequence homologies between their RNAs indicates that helper virus is not the origin of satellite virus.

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What other subviral entities infect animal cells?

• HDV is only viroid like organism infecting animal cells

Other subviral entities

~agents responsible for the spongiform encephalopathies

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~ kuru and creutzfeldt-Jakob disease in human

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~ scrapie in sheep (Prion) &

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+ bovine spongiform encephalopathy 

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Prions

Iinfectious agents composed exclusively of a single sialoglycoprotein called PrP 27-30.

- contain no nucleic acid.

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- composed of 145 amino acids

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Prion Diseases

• Animals

• Scrapie: sheep

• TME (transmissible mink encephalopathy): mink

• CWD (chronic wasting disease): mule, deer, elk

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• BSE (bovine spongiform encephalopathy): cows

• Humans –

- CJD: Creutzfeld-Jacob Disease

- GSS: Gerstmann-Straussler-Scheinker syndrome

- FFI: Fatal Familial Insomnia

- Kuru

- Alpers Syndrome

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What is the origin of various types of subcellular entities?

- Intrigued question for scientist (????????) .

• - No fossils of viral entities have ever been identified

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• - Evolutionary homology or convergent evolution

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Three theories

• ~ Two theories assume that viruses arose after their host cells evolve

~ have an more ancient origin than the host cells.

1)   Regressive theory _ degenerated progeny of other obligatory intracellular parasites

2)   Cellular constituent theory – develop after their host cells

3)   Endosymbiotic theory –began as bacteria & gradually loss their genomes

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Virus Replication

• Viral populations do not grow through cell division, because they are acellular; instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves.
• A virus can still cause degenerative effects within a cell without causing its death; collectively these are termed cytopathic effects.

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Virus life cycle

• The life cycle of viruses differs greatly between species (see below) but there are six basic stages in the life cycle of viruses:

Virus Replication

Basic six steps are more clearly divided into nine steps

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• 1. Adsorption/attachment
• 2. Penetration
• 3. Uncoating
• 4. Transcription
• 5. Translation
• 6. Processing
• 7. Replication
• 8. Assembling
• 9. Budding/lysis

Virus Replication

• Attachment:
• Specific binding between viral capsid proteins and specific receptors on the host cellular surface.

* This specificity determines the host range of a virus.

* For example, the human immunodeficiency virus (HIV) infects only human T cells, because its surface protein, gp120, can interact with CD4 and receptors on the T cell's surface.

• Attachment to the receptor can induce the viral-envelope protein to undergo changes that results in the fusion of viral and cellular membranes.
• Penetration:
• Following attachment, viruses enter the host cell through receptor mediated endocytosis or membrane fusion.
• Uncoating:
• Process that viral capsid is removed is degraded by viral enzymes or host enzymes thus releasing the viral genomic nucleic acid.

Virus Replication

• Protein synthesis and assembly:
• Involves synthesis of viral messenger RNA (mRNA) for viruses except positive sense RNA viruses, and assembly of viral proteins and viral genome replication.

• Maturation:
• Following the assembly of the virus particles post-translational modification of the viral proteins often occurs. In viruses such as HIV, this modification), occurs after the virus has been released from the host cell.

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• Release:
• Viruses are released from the host cell by lysis. Enveloped viruses (e.g., HIV) typically are released from the host cell by “budding”. During this process, the virus acquires its phospholipid envelope which contains embedded viral glycoproteins.

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DNA viruses

• Animal DNA viruses, such as herpesviruses, enter the host via endocytosis, the process by which cells take in material from the external environment.

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• Frequently after a chance collision with an appropriate surface receptor on a cell, the virus penetrates the cell, the viral genome is released from the capsid and host polymerases begin transcribing viral mRNA.

• New virions are assembled and released either by cell lysis or by budding off the cell membrane.

RNA viruses

• Animal RNA viruses can be placed into about four different groups depending on their modes of replication.

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• The polarity of the RNA largely determines the replicative mechanism, as well as whether the genetic material is single-stranded or double-stranded.

• Some RNA viruses are actually DNA based but use an RNA-intermediate to replicate.

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• RNA viruses are dependent on virally encoded RNA replicase to create copies of their genomes.

Reverse transcribing viruses

• Reverse transcribing viruses replicate using reverse transcription, which is the formation of DNA from an RNA template.

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• Viruses containing RNA genomes use a DNA intermediate to replicate, whereas those containing DNA genomes use an RNA intermediate during genome replication.

• Both types use the reverse transcriptase enzyme to carry out the nucleic acid conversion.

Bacteriophages

• Transmission electron micrograph of multiple bacteriophages attached to a bacterial cell wall

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• Bacteriophages infect specific bacteria by binding to surface receptor molecules and then enter the cell.

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• Within a short amount of time, in some cases, just minutes, bacterial polymerase starts translating viral mRNA into protein.

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• These proteins go on to become either new virions within the cell, helper proteins which help assembly of new virions, or proteins involved in cell lysis.

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• Viral enzymes aid in the breakdown of the cell membrane