Questions: Viral Classification and Genomic Organization

Question 1

Researchers isolate a novel virus with a negative-sense single-stranded RNA genome. Before conducting any further experiments, they can predict that this virus:

• A. Can use its genome directly as mRNA for immediate translation by host ribosomes
• B. Must carry its own RNA-dependent RNA polymerase inside the virion to transcribe the negative-sense genome into mRNA
• C. Must use reverse transcriptase to convert its RNA genome into a DNA intermediate before replication
• D. Can use host cell RNA polymerase to transcribe its genome directly into mRNA

Answer: (B)

Host cells contain no enzyme capable of reading negative-sense RNA — all cellular polymerases use DNA templates or positive-sense RNA. A negative-sense ssRNA virus (Baltimore Group V) must therefore package its own RNA-dependent RNA polymerase inside the virion, ready to transcribe the genome into positive-sense mRNA upon cell entry. This prediction follows directly from genome type alone. Influenza virus and rabies virus exemplify this: their virions carry their own RdRp because the host provides nothing that can read a negative-sense template.

Question 2

A positive-sense ssRNA virus differs from a negative-sense ssRNA virus in that:

• A. The positive-sense genome can serve directly as mRNA for translation, while negative-sense RNA must first be converted to its complementary strand to produce mRNA
• B. Positive-sense viruses are always enveloped while negative-sense viruses lack an envelope
• C. Positive-sense viruses exclusively infect plants while negative-sense viruses primarily infect animals
• D. Positive-sense viruses use host ribosomes while negative-sense viruses carry their own ribosomes in the virion

Answer: (A)

The polarity of the genome determines the first and most critical step after cell entry. Positive-sense ssRNA (Group IV) has the same sequence as mRNA, so host ribosomes can translate it directly — the naked genome is itself infectious. Negative-sense ssRNA (Group V) is the complement of mRNA and must be transcribed into positive-sense mRNA by a virion-packaged polymerase before any protein can be made. This single difference has cascading implications for replication strategy, drug targeting, and the minimum gene content the virion must carry.

Question 3

The Baltimore classification system groups viruses primarily according to their host range and whether they possess a lipid envelope.

• T. True
• F. False

Answer: False

Baltimore classification groups viruses by genome type and replication strategy — specifically, by how the virus gets from its genome to mRNA. The seven groups are based on whether the genome is DNA or RNA, single- or double-stranded, positive- or negative-sense, and whether replication proceeds through a reverse transcription step. Host range and envelope status are important features of viral biology but are not the basis of Baltimore grouping. Knowing the Baltimore group tells you the minimum enzymatic steps between genome and protein production, which is far more mechanistically informative.

Question 4

If the isolated RNA of a positive-sense ssRNA virus is injected directly into a host cell without any viral proteins, the cell can produce viral proteins.

• T. True
• F. False

Answer: True

Positive-sense ssRNA has the same sequence as mRNA, so host ribosomes can translate it immediately without any viral enzyme. The naked RNA is therefore infectious — experimentally demonstrated with poliovirus and tobacco mosaic virus RNA. In contrast, injecting naked negative-sense ssRNA produces nothing because the cell has no enzyme to read it. This asymmetry explains why positive-sense RNA viruses can encode their polymerase as a regular protein (made after cell entry), while negative-sense viruses must carry polymerase pre-packaged in the virion.

Question 5

Why is Baltimore classification described as predictive rather than merely a naming convention? Give a specific example.

Model answer: Baltimore classification predicts what enzymatic machinery a virus must carry, based solely on genome type. The host cell can only translate mRNA, so every virus must bridge from its genome to mRNA. A Group V virus (negative-sense ssRNA) cannot use any host enzyme for this step, so it must package its own RNA-dependent RNA polymerase in the virion — a prediction you can make from genome type alone, before any biochemistry. A Group IV virus (positive-sense ssRNA) can use host ribosomes directly, so its naked RNA is infectious and it need not package a polymerase.

The predictive power is particularly valuable when encountering novel pathogens. By sequencing enough of the genome to determine its type, virologists can immediately predict replication requirements, enzymatic needs, and potential drug targets before extensive characterization. This is why Baltimore classification is the first analytical framework applied to newly discovered viruses — it transforms sequence information into mechanistic predictions about biology, guiding both experimental design and antiviral drug target identification.