Fxck Lectures

Baltimore Classification System

Remember the viral structures we covered earlier—the capsid and the lipid envelope. Those structures protect the viral payload. But what exactly is that payload, and how does it hijack the host cell?

Viruses do not have their own ribosomes. To manufacture their proteins, they have to borrow the host cell’s machinery. The host ribosome only reads one language: messenger RNA (mRNA). So no matter what kind of genome a virus carries—DNA or RNA, single or double-stranded—it has to end up at the same destination: a positive-sense mRNA strand the host ribosome can translate.

This “all roads lead to mRNA” principle is the foundation of the Baltimore Classification System. It sorts every virus into one of seven classes based on the route its genome takes to reach that mRNA finish line. Look at the diagram on the slide—notice how the arrows from all seven classes converge on the central golden strand labeled “mRNA (+)”. That’s the mandatory destination.

Let’s walk through how each class gets there.

Class I — dsDNA. Double-stranded DNA viruses like Adenovirus and Herpesvirus. This is the same genomic language our own cells use, so the host’s own enzymes can transcribe it straight into mRNA. No special viral machinery required.

Class II — ssDNA. Single-stranded DNA, like Parvovirus. The virus first builds a complementary strand to form a dsDNA intermediate, then follows the Class I pathway. One extra step.

Class III — dsRNA. Double-stranded RNA, like Rotavirus. The host has no enzyme that reads RNA to make more RNA, so the virus has to bring its own RNA-dependent RNA polymerase packaged inside its capsid to transcribe its negative strand into positive-sense mRNA.

Class IV — +ssRNA. Positive-sense single-stranded RNA, like Poliovirus and SARS-CoV-2. A trick to recall this: “positive means ready to proceed.” This strand is functionally identical to mRNA. The moment it enters the cell, host ribosomes can translate it directly. No extra enzymes needed.

Class V — −ssRNA. Negative-sense single-stranded RNA, like Influenza and Rabies. This strand is the mirror image of mRNA—if a host ribosome looks at it, it sees gibberish. So the virus has to carry its own RNA-dependent RNA polymerase inside the capsid to transcribe the negative strand into a readable positive strand before translation can begin.

Class VI — +ssRNA retrovirus. This is HIV’s class. The genome looks like Class IV (+ssRNA) but the strategy is completely different. Instead of translating directly, the virus uses an enzyme called reverse transcriptase to convert its RNA backwards into double-stranded DNA. That viral DNA then physically integrates into the host’s own chromosome—the genome becomes part of the cell, hidden indefinitely.

Class VII — dsDNA reverse-transcribing. The mirror of Class VI. Hepatitis B is the example. The virus starts with dsDNA but uses an RNA intermediate and reverse transcription to replicate. Genome shape says DNA, replication mechanism says retrovirus.

The genome dictates the pathway, and the pathway dictates which specific enzymes the virus has to bring with it. That’s why Class V viruses like Influenza must pack a polymerase, and why Class VI retroviruses are the only ones we treat with reverse-transcriptase inhibitors—other classes don’t use that enzyme.