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Viral Life Cycles
Replication Strategies

Master the lytic and lysogenic cycles, understand how retroviruses replicate using reverse transcriptase, and learn the key differences between DNA and RNA viral strategies.

MCAT Biological Foundations

What Is a Virus?

A virus is an obligate intracellular parasite: it cannot replicate on its own. It must hijack a host cell's machinery to produce new viral particles. Viruses consist of a nucleic acid genome (DNA or RNA) enclosed in a protein capsid, and sometimes an outer lipid envelope.

Genome
DNA or RNA, single-stranded or double-stranded
Capsid
Protein coat that protects the genome
Envelope
Lipid bilayer derived from host membrane (some viruses)

Why Viral Replication Matters

Understanding viral life cycles is essential for the MCAT because it connects molecular biology, genetics, and immunology. Viral replication strategies explain how pathogens evade immune responses, cause disease, and serve as tools in biotechnology (e.g., gene therapy vectors).

Overview of Viral Life Cycles

Attachment Penetration Uncoating DECISION POINT LYTIC Biosynthesis (Replicate genome + proteins) Assembly (Package new virions) Lysis (Cell Death) LYSOGENIC Integration (Provirus / Prophage) Dormancy (Replicate with host DNA) Induction

The Lytic Cycle

In the lytic cycle, the virus immediately commandeers host machinery to replicate its genome and synthesize viral proteins. New virions are assembled, and the host cell is lysed (destroyed), releasing hundreds of progeny viruses.

1
Attachment: Viral surface proteins bind specific host cell receptors.
2
Penetration: Viral genome (+ enzymes) enters the host cell.
3
Biosynthesis: Host ribosomes, polymerases, and tRNAs are redirected to produce viral components.
4
Assembly: Capsid proteins self-assemble around newly replicated genomes.
5
Lysis: Viral enzymes (e.g., lysozyme in phages) break open the cell membrane, releasing virions.

The Lysogenic Cycle

In the lysogenic cycle, the viral genome integrates into the host chromosome (becoming a prophage or provirus). The viral DNA is replicated passively each time the host cell divides. The virus remains dormant until environmental stress triggers induction, switching to the lytic cycle.

Prophage
Integrated bacteriophage DNA within the bacterial chromosome
Provirus
Integrated viral DNA in a eukaryotic host genome (e.g., HIV)

Lytic vs. Lysogenic

Lytic Cycle Lysogenic Cycle
Host Cell Fate Destroyed (lysis) Survives
Viral DNA Free in cytoplasm Integrated into host chromosome
Replication Immediate, active Passive (with host DNA)
Viral Term Virulent phage Temperate phage
Example T4 bacteriophage Lambda (\(\lambda\)) phage
Trigger Immediate upon infection Induction by UV, stress

Retroviral Replication Strategy

Retroviruses (e.g., HIV) carry an RNA genome and the enzyme reverse transcriptase. After entry, the RNA is converted into double-stranded DNA, which integrates into the host genome via integrase. This integrated DNA is called a provirus.

ssRNA Viral genome RT dsDNA cDNA copy Integrase Provirus In host genome Host pol mRNA Transcribed Translation Viral proteins + enzymes Genomic RNA New viral genomes Assembly + Budding

Reverse Transcriptase: Key Enzyme

Reverse transcriptase (RT) is an RNA-dependent DNA polymerase. It synthesizes DNA from an RNA template, violating the traditional "central dogma" flow. RT has three enzymatic activities:

1
RNA-dependent DNA polymerase: Uses viral ssRNA as a template to synthesize a complementary DNA (cDNA) strand.
2
RNase H activity: Degrades the RNA strand of the RNA:DNA hybrid.
3
DNA-dependent DNA polymerase: Synthesizes the second DNA strand using the first cDNA as template, producing dsDNA.

DNA vs. RNA Virus Strategies

DNA Viruses RNA Viruses
Genome dsDNA (usually) ssRNA or dsRNA
Replication Site Nucleus (most) Cytoplasm (most)
Polymerase Used Host DNA polymerase Viral RNA-dependent RNA polymerase
Mutation Rate Lower (proofreading) Higher (no proofreading)
Examples Herpes, Adenovirus, Pox Influenza, HIV, SARS-CoV-2
Exception Poxvirus: replicates in cytoplasm Influenza: replicates in nucleus

The Baltimore Classification

The Baltimore Classification groups viruses into seven classes based on their genome type and path to mRNA. Every virus must produce mRNA that host ribosomes can translate: the classification describes how they get there.

mRNA (+) sense I: dsDNA Herpes II: ssDNA Parvovirus III: dsRNA Reovirus IV: (+)ssRNA Coronavirus V: (-)ssRNA Influenza VI: ssRNA-RT HIV VII: dsDNA-RT Hepatitis B

(+) Sense vs. (-) Sense RNA

(+) Sense RNA
Can be directly translated by host ribosomes as mRNA. Functions immediately upon entry. Examples: Poliovirus, SARS-CoV-2.
(-) Sense RNA
Must first be converted to (+) sense mRNA by viral RNA-dependent RNA polymerase (RdRp), which the virus must carry. Examples: Influenza, Ebola.

How to Approach Viral Replication Problems

1
Identify the genome type: Is it DNA or RNA? Single-stranded or double-stranded? (+) or (-) sense?
2
Determine the path to mRNA: Can the genome serve directly as mRNA, or does it need conversion first?
3
Identify the replication site: Nucleus (most DNA viruses, influenza) or cytoplasm (most RNA viruses, poxvirus)?
4
Check for special enzymes: Does the virus carry reverse transcriptase, integrase, or its own RNA polymerase?
5
Determine lytic vs. lysogenic: Does the virus immediately replicate (lytic/virulent) or integrate and wait (lysogenic/temperate)?

Example: Lambda Phage Decision

Lambda (\(\lambda\)) phage infects E. coli. Upon entry, two competing genetic programs activate: the lytic pathway (controlled by gene cro) and the lysogenic pathway (controlled by gene cI). Which wins depends on environmental conditions.

Lytic: Cro Protein
Represses cI gene, allowing lytic genes to be expressed. Favored under stress (UV damage, nutrient deprivation).
Lysogenic: cI Repressor
Represses lytic genes, promotes integration. Favored in healthy, dividing host cells.

Example: HIV Replication Cycle

1
Binding: gp120 binds CD4 receptor on T-helper cells, then a coreceptor (CCR5 or CXCR4).
2
Fusion + Entry: gp41 mediates membrane fusion; viral core enters the cytoplasm.
3
Reverse Transcription: RT converts ssRNA to dsDNA in the cytoplasm.
4
Integration: Viral integrase inserts dsDNA into host chromosome (provirus).
5
Transcription + Translation: Host RNA polymerase II transcribes provirus; host ribosomes translate viral proteins.
6
Assembly + Budding: New virions assemble at the membrane and bud off, acquiring the lipid envelope. Protease cleaves polyproteins into functional units.

Antiviral Drug Targets

Understanding the viral life cycle reveals specific drug targets at each step. The MCAT may ask you to identify which enzyme or process a given antiviral inhibits.

NRTIs / NNRTIs
Block reverse transcriptase: NRTIs are chain terminators; NNRTIs bind an allosteric site
Protease Inhibitors
Prevent protease from cleaving polyproteins into functional viral proteins
Integrase Inhibitors
Block integrase from inserting viral DNA into the host genome
Entry Inhibitors
Block gp120/gp41 interaction with CD4/coreceptors; prevent fusion

Common Mistakes

✕ Confusing Sense
Thinking (-) sense RNA can be translated directly. It cannot: it must first be copied into (+) mRNA by an RNA-dependent RNA polymerase.
✕ Forgetting Exceptions
Assuming all DNA viruses replicate in the nucleus and all RNA viruses in the cytoplasm. Remember poxvirus (cytoplasm) and influenza (nucleus).
✕ Mixing Up RT Activities
Thinking reverse transcriptase only makes DNA from RNA. It also has RNase H and DNA-dependent DNA polymerase activities.

Summary: Viral Strategies at a Glance

Feature Lytic Lysogenic Retroviral
Genome Fate Replicated freely Integrated (prophage) RNA to dsDNA to provirus
Key Enzyme Host polymerases Recombinase Reverse transcriptase
Host Cell Destroyed Survives Survives (initially)
Mutation Rate Moderate Low (dormant) Very high
Classic Example T4 phage \(\lambda\) phage HIV

Question 1 of 5

A temperate bacteriophage infects a bacterial cell and its DNA becomes incorporated into the host chromosome. This integrated viral DNA is called a:

Question 2 of 5

Which of the following is NOT an enzymatic activity of HIV reverse transcriptase?

Question 3 of 5

A researcher discovers a new virus with a (-) sense single-stranded RNA genome. Which statement about this virus must be true?

Question 4 of 5

During HIV infection, the viral enzyme integrase performs which function?

Question 5 of 5

Poxvirus is a dsDNA virus that replicates in the cytoplasm of host cells. What does this imply about poxvirus?