Why must negative-sense ssRNA viruses (Baltimore Group V) package their own RNA-dependent RNA polymerase inside the virion?
ATheir RNA genome is too large to be directly translated by host ribosomes
BTheir genome cannot serve as mRNA directly and must first be transcribed into a complementary positive-sense strand before translation can occur
CHost cells recognize and degrade negative-sense RNA before it can reach the ribosome
DNegative-sense RNA is chemically unstable outside the viral capsid and must be immediately copied
Host ribosomes translate positive-sense RNA (5'→3' directionality matching mRNA). Negative-sense RNA is the complementary strand — it cannot be translated directly. The virus must therefore transcribe it into positive-sense mRNA before protein synthesis can begin. But the host cell has no RNA-dependent RNA polymerase (it doesn't need one — its own transcription uses DNA templates). So the virus must carry its own RdRp into the cell inside the virion. This is why negative-sense RNA viruses are unique in requiring a packaged polymerase as a structural component.
Question 2 Multiple Choice
A student classifying a newly discovered virus notes its icosahedral capsid and lack of envelope, and concludes it belongs to the same Baltimore group as influenza. What is wrong with this reasoning?
ANothing — capsid geometry is the primary basis of the Baltimore classification
BThe Baltimore classification is based on genome type and the path to mRNA production, not structural features like capsid shape or envelope status
CThe classification should be based on genome size rather than capsid shape
DInfluenza actually has an icosahedral capsid, so the structural comparison is valid
The Baltimore system classifies viruses by replication strategy — specifically, how they produce mRNA. Influenza is a negative-sense ssRNA virus (Group V) with a segmented RNA genome packaged in a helical, enveloped virion. A non-enveloped icosahedral virus could be in any of the seven Baltimore groups depending on its genome type. Structural features like capsid geometry and envelope are important for a complete classification but are orthogonal to the Baltimore grouping, which specifically captures the relationship between the genome and mRNA production.
Question 3 True / False
A positive-sense ssRNA virus can use its genomic RNA directly as mRNA upon entering the host cell, without requiring any virion-packaged polymerase.
TTrue
FFalse
Answer: True
This is the defining feature of Group IV (positive-sense ssRNA) viruses. Their genome has the same polarity as mRNA — it can be directly loaded onto host ribosomes and translated immediately upon cell entry. Poliovirus and SARS-CoV-2 are examples. This is why positive-sense RNA viruses are often experimentally convenient: purified genomic RNA can initiate infection on its own (it is 'infectious RNA'). Contrast with negative-sense RNA viruses, which require a packaged polymerase, or retroviruses, which require reverse transcriptase.
Question 4 True / False
RNA viral genomes can in principle grow as large as DNA viral genomes, since genome size is limited primarily by the physical capacity of the viral capsid.
TTrue
FFalse
Answer: False
RNA polymerases lack proofreading activity, leading to error rates roughly 10⁴–10⁶ times higher than DNA polymerases. For large RNA genomes, the resulting mutation rate per replication cycle would accumulate so many errors that most progeny genomes would be non-functional — a phenomenon called error catastrophe. This sets a size ceiling of roughly 30 kb for RNA genomes. Coronaviruses push this limit by encoding a rare exonuclease proofreading function. DNA polymerases proofread, so DNA viruses can support much larger genomes; Mimivirus exceeds 1 Mb.
Question 5 Short Answer
Why does the Baltimore classification system organize viruses by their path to mRNA production rather than by structural features like capsid shape or envelope, and why is this more biologically useful?
Think about your answer, then reveal below.
Model answer: Every virus must produce mRNA that host ribosomes can translate — this is the universal constraint that defines viral replication. The path from genome to mRNA determines what enzymes the virus must encode, what host machinery it can exploit, and what drug targets are available. Structural features like capsid shape tell you about transmission and immune recognition, but the genome type tells you how the virus operates as a molecular machine.
The practical utility is immediate: knowing a virus is in Baltimore Group V tells you it must package an RdRp (potential drug target), that its genome is anti-sense (affects how you design detection probes), and that it must synthesize mRNA before any protein can be made (affects the kinetics of infection). Knowing it has a helical capsid tells you much less about its biology. The Baltimore system was revolutionary because it provided a mechanistic, not just descriptive, framework — organizing diversity around a universal biological principle rather than appearance.