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How Viruses Enter Cells, Replicate, and Evade Immunity

1Viral Architecture and the Logic of the Life Cycle2Attachment and Entry: Crossing the Membrane3Genome Replication and Gene Expression4Assembly, Egress, and Transmission5Innate Immune Detection of Viral Infection6Adaptive Immunity: Antiviral Antibodies and T Cells7Immune Evasion Strategies8From Mechanism to Intervention: Antivirals and Vaccines
Viral Architecture and the Logic of the Life Cycle

Genome Type Decides the Replication Strategy

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The organizing question is simple: can the host ribosome read this genome directly? Ribosomes read positive-sense single-stranded RNA. If the genome is already in that form, translation can start immediately and the virus does not need to carry a polymerase. If the genome is negative-sense, it is the mirror image of mRNA and cannot be read, so the particle must carry an RNA-dependent RNA polymerase to make a readable copy. Double-stranded RNA has the same problem. Now look at the right side of the diagram. DNA viruses generally work in the nucleus, where the host keeps its polymerases and nucleotides. Reverse-transcribing viruses go further: they copy RNA into DNA and insert it into a host chromosome, which also requires the nucleus. Follow the arrows and notice that each genome type lands on a specific combination of packaged enzyme and cellular compartment. That combination is the replication strategy.
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The single most useful classification of viruses is by genome. The Baltimore scheme groups viruses by how their genome is converted into messenger RNA, because every virus must produce mRNA that the host ribosome can read. The host ribosome only reads single-stranded RNA in the positive sense — the same sense as mRNA. Anything else has to be converted first, and the conversion step determines where replication happens and what the virus must carry with it.

A positive-sense single-stranded RNA genome can be translated directly by ribosomes the moment it enters the cytoplasm. No packaged polymerase is strictly required, because the first protein made can be the polymerase itself. A negative-sense RNA genome is the complement of mRNA, so it cannot be translated; the virus must package an RNA-dependent RNA polymerase to copy it into positive-sense mRNA. Double-stranded RNA genomes face the same problem and also package a polymerase, typically inside the capsid.

DNA viruses generally replicate in the nucleus, where host DNA and RNA polymerases and the nucleotide pool are available. Most DNA viruses use host polymerases for at least part of their transcription, though large DNA viruses often encode some of their own replication enzymes. Reverse-transcribing viruses carry the machinery to copy RNA into DNA and then integrate that DNA into the host chromosome, which requires nuclear access.

Segmented genomes — genomes split into separate nucleic acid molecules — allow reassortment, the swapping of whole segments between related viruses. That is a distinct mechanism from mutation and becomes important later when we discuss antigenic shift.

A practical rule: if the genome cannot be read directly by a ribosome, the virus must bring or immediately build the enzyme that makes it readable, and that constraint shapes where in the cell the whole process unfolds.

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