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USMLE Step 1MicrobiologyEP 10 of 14

DNA vs RNA virus replication: which enzyme each genome needs

Where DNA and RNA viruses replicate, what positive-sense and negative-sense mean, and the one rule that tells you which enzyme a virion must carry.

  • 5:48 video
  • 3 min read
  • 19 sources
  • Published 15 Nov 2026
Video lesson · 5:48 · Watch on YouTubeSeries: Microbiology · @medservatory
Chapters (13)
By the end of this lesson

Explain where DNA and RNA viruses replicate and why positive-sense, negative-sense and retroviral genomes need different enzymes.

The short version

  1. Most DNA viruses replicate in the nucleus and use the host's RNA polymerase to make their messenger RNA; poxviruses replicate in the cytoplasm and carry their own DNA-dependent RNA polymerase.
  2. A positive-sense RNA genome (other than a retrovirus) is already messenger RNA, so the RNA alone can start an infection.
  3. Negative-sense and double-stranded RNA viruses carry an RNA-dependent RNA polymerase in the virion.
  4. Retroviruses are positive-sense but carry reverse transcriptase, then integrate a DNA copy into the host chromosome.
  5. The rule: the virion carries the enzyme the host cannot supply.

Why one naked RNA genome works and another does not

Take the RNA out of a poliovirus particle and put it, on its own, into a cell. The cell makes new virus. Do the same with RNA from an influenza virus and nothing happens. The reason lies in how each genome is read.[1][3][4]

Both are viral RNA, so why does one work alone and the other fail? The answer is the heart of DNA vs RNA virus replication: each genome type needs a particular enzyme, and the cell does not always supply it.[1]

The flow of information: positive-sense and negative-sense RNA

A cell follows one flow of information: DNA to RNA to protein. Ribosomes read messenger RNA. A strand with that same sense is called positive-sense, and a strand complementary to it is called negative-sense.[1][2][3]

For gene expression, cells make RNA from DNA but do not copy RNA from RNA or make DNA from RNA. So a virus has to bring or encode whatever its genome needs that the cell cannot supply.[1]

DNA virus replication: the nucleus, and the poxvirus exception

Most DNA viruses replicate in the nucleus, where the host's RNA polymerase makes their messenger RNA. Adenovirus is an example.[1][2][5]

The exception is the poxviruses. They replicate in the cytoplasm, away from the host polymerases, so they encode and package their own DNA-dependent RNA polymerase.[1][6][7]

Hepatitis B is a DNA virus with a twist: it makes an RNA copy and then reverse transcribes it. It returns in a later lesson.[8][9]

DNA viruses: where they replicate and what the virion carries
VirusReplication sitePolymerase source
Adenovirus (most DNA viruses)NucleusHost RNA polymerase makes the mRNA; none carried
PoxvirusesCytoplasmOwn DNA-dependent RNA polymerase, packaged in the virion
Hepatitis BNot covered here; covered in a later lessonOwn polymerase with reverse transcriptase activity: makes an RNA copy, then reverse transcribes it

RNA virus replication: positive-sense, negative-sense and double-stranded

With a few exceptions, RNA viruses replicate in the cytoplasm. Influenza replicates in the nucleus, and retroviruses send a DNA copy there.[1][10][11]

Positive-sense single-stranded RNA viruses, such as poliovirus, have a genome that is already messenger RNA. Ribosomes translate it at once, and one of the first proteins made is the viral RNA-dependent RNA polymerase (RdRp). So the RNA alone can start an infection.[1][3][12]

Negative-sense single-stranded RNA viruses, such as influenza, have a genome that ribosomes cannot read. The virion must carry its own RdRp to copy the genome into positive-sense messenger RNA. Naked, the RNA is silent.[1][4][19]

Double-stranded RNA viruses, such as rotavirus, also carry an RdRp in the core, to make messenger RNA from the genome.[1][13]

Worked example: the opening pair
  1. Poliovirus genome is positive-sense, so it is already messenger RNA
  2. Ribosomes translate it at once, and RdRp is among the first proteins made
  3. Result: the naked RNA can start an infection
  4. Influenza genome is negative-sense, so ribosomes cannot read it
  5. The virion must carry its own RdRp to copy the genome into messenger RNA
  6. Result: the naked RNA is silent

Retroviruses: reverse transcriptase and integration

Retroviruses, such as HIV, have a positive-sense genome, but it is not translated first. The virion carries reverse transcriptase, which copies the RNA into DNA.[1][11][14]

That DNA integrates into the host chromosome, and the host's own polymerases take over.[1][11][14]

The rule: the virion carries the enzyme the host cannot supply

The rule that ties the lesson together: the virion carries the enzyme the host cannot supply.[1]

Which enzyme the virion carries
Virus groupExampleCarried in the virion
DNA virus replicating in the cytoplasmPoxvirusDNA-dependent RNA polymerase
Negative-sense ssRNAInfluenzaRNA-dependent RNA polymerase
Double-stranded RNARotavirusRNA-dependent RNA polymerase
RetrovirusHIVReverse transcriptase
Positive-sense RNA, other than retrovirusesPoliovirusNone: the genome is the message
Most DNA virusesAdenovirusNone: the nucleus supplies it

Positive-sense RNA viruses other than retroviruses carry no polymerase because their genome is the message. Most DNA viruses carry none because the nucleus supplies it.[1][2][3]

Practice question

Original · USMLE style
Your turnQB-MS-S1-MICRO-006-01

A 2-year-old boy has a barking cough and inspiratory stridor. Nasopharyngeal culture grows parainfluenza virus, an enveloped single-stranded RNA virus that replicates in the cytoplasm. In the laboratory, genomic RNA purified from the virions is placed in cultured cells. No viral proteins are made, and no progeny appear.

Which of the following enzymes must the intact virion carry to begin infection?
Pick one option. Your answers stay on this device.

Common questions

Where do DNA and RNA viruses replicate?

Most DNA viruses replicate in the nucleus, with poxviruses as the exception in the cytoplasm. With a few exceptions RNA viruses replicate in the cytoplasm; influenza replicates in the nucleus, and retroviruses send a DNA copy there.

What is the difference between positive-sense and negative-sense RNA?

A positive-sense strand has the same sense as messenger RNA, so ribosomes can read it. A negative-sense strand is complementary to messenger RNA, so ribosomes cannot read it until it is copied.

Why is naked positive-sense RNA infectious but negative-sense RNA is not?

A positive-sense genome (other than a retrovirus) is already messenger RNA and encodes its own RdRp, so translation can start at once. A negative-sense genome needs an RdRp that only the virion carries.

Which viruses carry their own polymerase in the virion?

Poxviruses carry a DNA-dependent RNA polymerase, negative-sense and double-stranded RNA viruses carry an RNA-dependent RNA polymerase, and retroviruses carry reverse transcriptase. Hepatitis B also packages its own polymerase with reverse transcriptase activity; it is covered in a later lesson.

Why are retroviruses an exception among positive-sense viruses?

Their genome is positive-sense, but it is not translated first. The virion carries reverse transcriptase, which copies the RNA into DNA that integrates into the host chromosome.

Transcript

Read the full narration, by chapter676 words

0:00Same RNA, one works alone: the hook

Take the RNA out of a poliovirus particle and put it, on its own, into a cell. The cell makes new virus. Do the same with RNA from an influenza virus, and nothing happens. Both are viral RNA. Why does one work alone and the other fail? Today: where DNA and RNA viruses replicate, and why each genome type needs its own enzymes.

0:25The flow of information: positive-sense and negative-sense

A cell follows one flow of information: DNA to RNA to protein. Ribosomes read messenger RNA, and a strand with that same sense is called positive-sense. A strand complementary to it is called negative-sense. Cells make RNA from DNA, but for gene expression they do not copy RNA from RNA or make DNA from RNA. So a virus has to bring or encode whatever its genome needs that the cell cannot supply.

0:58DNA viruses: nucleus, and the poxvirus exception

First, DNA viruses. Most replicate in the nucleus, using the host's own polymerases. Adenovirus is an example. The exception is the poxviruses. They replicate in the cytoplasm, away from the host polymerases, so they package their own DNA-dependent RNA polymerase.

1:20Hepatitis B: a DNA virus with a twist

Hepatitis B is a DNA virus with a twist: it makes an RNA copy and then reverse transcribes it. We meet it again in a later lesson.

1:31RNA viruses: cytoplasm, with exceptions

Now RNA viruses. With a few exceptions, they replicate in the cytoplasm. Influenza replicates in the nucleus, and retroviruses send a DNA copy there.

1:42Positive-sense RNA: poliovirus

Positive-sense single-stranded RNA viruses, such as poliovirus, have a genome that is already messenger RNA. Ribosomes translate it at once, and one of the first proteins made is the viral RNA-dependent RNA polymerase. So the RNA alone can start an infection. That was our poliovirus.

2:04Negative-sense RNA: influenza carries its own RdRp

Negative-sense single-stranded RNA viruses, such as influenza, have a genome that ribosomes cannot read. The virion must carry its own RNA-dependent RNA polymerase, to copy the genome into positive-sense messenger RNA. Naked, the RNA is silent. That was our influenza.

2:26Double-stranded RNA: rotavirus

Double-stranded RNA viruses, such as rotavirus, also carry an RNA-dependent RNA polymerase in the core, to make messenger RNA from the genome.

2:38Retroviruses: reverse transcriptase and integration

Retroviruses, such as HIV, have a positive-sense genome, but it is not translated first. The virion carries reverse transcriptase, which copies the RNA into DNA. That DNA integrates into the host chromosome, and the host's own polymerases take over.

2:57The rule: the virion carries the enzyme the host cannot supply

So the rule is this: the virion carries the enzyme the host cannot supply. Poxvirus: a DNA-dependent RNA polymerase. Negative-sense and double-stranded RNA viruses: an RNA-dependent RNA polymerase. Retroviruses: reverse transcriptase. Positive-sense RNA viruses other than retroviruses carry no polymerase, because their genome is the message. Most DNA viruses carry none, because the nucleus supplies it.

3:31Your turn: a practice question

Your turn. A 2-year-old boy has a barking cough and inspiratory stridor. Nasopharyngeal culture grows parainfluenza virus, an enveloped single-stranded RNA virus that replicates in the cytoplasm. In the laboratory, genomic RNA purified from the virions is placed in cultured cells. No viral proteins are made, and no progeny appear. Which of the following enzymes must the intact virion carry to begin infection? A, DNA-dependent DNA polymerase. B, DNA-dependent RNA polymerase. C, RNA-dependent DNA polymerase. D, RNA-dependent RNA polymerase. E, integrase. Pause here and decide.

4:24The answer, one option at a time

A is out: that enzyme copies DNA genomes, and this virus has an RNA genome with no DNA stage. B is out: a virion carries that enzyme when it has a DNA genome that replicates outside the nucleus, as poxviruses do. C is out: that is reverse transcriptase, which retroviruses use to make DNA, and this virus never makes any. E is out: integrase joins viral DNA to the host chromosome, again a retroviral step. So the answer is D. Parainfluenza virus is negative-sense, ribosomes cannot read its genome, and so the virion carries its own RNA-dependent RNA polymerase to make messenger RNA.

5:12Recap pocket card and next lesson

Three things to keep. One: most DNA viruses replicate in the nucleus; poxviruses replicate in the cytoplasm and carry their own polymerase. Two: positive-sense RNA is already messenger; negative-sense and double-stranded RNA viruses carry an RNA-dependent RNA polymerase. Three: retroviruses carry reverse transcriptase and integrate into the host chromosome. Next, the HIV life cycle and the drugs that target it.

Sources

Numbers in the text, e.g. [1], point here
  1. OpenStax Microbiology. 6.2 The Viral Life Cycle. openstax.org/books/microbiology/pages/6-2-the-viral-life-cycle
  2. Wikipedia. Baltimore classification. en.wikipedia.org/wiki/Baltimore_classification
  3. Wikipedia. Positive-strand RNA virus. en.wikipedia.org/wiki/Positive-strand_RNA_virus
  4. Wikipedia. Negative-strand RNA virus. en.wikipedia.org/wiki/Negative-strand_RNA_virus
  5. Wikipedia. Adenoviridae. en.wikipedia.org/wiki/Adenoviridae
  6. Wikipedia. Poxviridae. en.wikipedia.org/wiki/Poxviridae
  7. Lumpy skin disease virus review. Animals 2025 (poxvirus transcription machinery). europepmc.org/article/PMC/PMC12606776
  8. Wikipedia. Hepatitis B. en.wikipedia.org/wiki/Hepatitis_B
  9. Hepatitis B virus review, 2026. europepmc.org/article/PMC/PMC13696948
  10. Wikipedia. Orthomyxoviridae. en.wikipedia.org/wiki/Orthomyxoviridae
  11. Wikipedia. Retrovirus. en.wikipedia.org/wiki/Retrovirus
  12. Wikipedia. Poliovirus. en.wikipedia.org/wiki/Poliovirus
  13. Wikipedia. Rotavirus. en.wikipedia.org/wiki/Rotavirus
  14. Wikipedia. HIV. en.wikipedia.org/wiki/HIV
  15. Wikipedia. Human parainfluenza viruses. en.wikipedia.org/wiki/Human_parainfluenza_viruses
  16. Wikipedia. Paramyxoviridae. en.wikipedia.org/wiki/Paramyxoviridae
  17. Wikipedia. Croup. en.wikipedia.org/wiki/Croup
  18. Croup paper, 2026. europepmc.org/article/PMC/PMC13270533
  19. Negative-strand RNA virus nucleocapsid as the functional template. europepmc.org/article/PMC/PMC13118897

The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.

Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (recoloured, outlined, resized): influenza virus, adenovirus, hepatitis virus, HIV. Illustrations: NIAID NIH BioArt Source (bioart.niaid.nih.gov), public domain, adapted: hepatocyte (used as a generic host cell), ribosome, RNA polymerase, retrovirus (BioArt items 202, 448, 729, 447). Icons: poxvirus icon by Bruno Hernaez via bioicons.com, CC0. The host cell outline, RNA strands, DNA helix, capsid sketches, rotavirus cross-section, chromosome, table, question card, recap and all handwriting are drawn in code (original). No AI-generated teaching images.

Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-MICRO-006.

For exam study only, not medical advice. Read the medical disclaimer.

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  9. EP 09Beta-lactamase and antibiotic resistance: three ways bacteria win5:13
  10. EP 10DNA vs RNA virus replication: which enzyme each genome needs5:48
  11. EP 11HIV life cycle and drug targets, step by step5:39
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