The viral replication cycle is the sequence of events a virus undergoes to infect a host cell, replicate its genome, assemble new virions, and spread to new cells. While specific details vary among virus families, the general steps are universal.

Step 1: Attachment (Adsorption)

Viral surface proteins (ligands) bind specifically to receptor molecules on the host cell surface, and the specificity of this interaction determines host range and tissue tropism. For example, HIV gp120 binds CD4 and co-receptors (CXCR4/CCR5) on T cells, while influenza hemagglutinin binds sialic acid residues on respiratory epithelial cells.

Step 2: Entry (Penetration)

Direct fusion occurs when the viral envelope fuses with the host cell membrane, releasing the capsid into the cytoplasm, as used by HIV, influenza, and herpesviruses. In receptor-mediated endocytosis, the virus-receptor complex is internalized in a clathrin-coated vesicle, and low pH in the endosome triggers fusion or uncoating, as used by adenovirus and flavivirus. Translocation is used by naked viruses that inject their genome through the cell membrane, as seen with bacteriophages.

Step 3: Uncoating

The viral capsid dissociates or is degraded by host enzymes, releasing the viral genome into the appropriate cellular compartment (nucleus for most DNA viruses, cytoplasm for most RNA viruses). The timing and location of uncoating are critical for successful replication.

Step 4: Replication and Transcription

DNA viruses typically replicate in the nucleus using host DNA-dependent RNA polymerase for transcription and viral or host DNA polymerase for genome replication. RNA viruses replicate in the cytoplasm using virus-encoded RNA-dependent RNA polymerase (RdRp), as host cells lack enzymes for RNA replication. Retroviruses convert RNA to DNA via reverse transcriptase, then integrate into the host genome as a provirus.

Step 5: Assembly (Maturation)

Viral structural proteins and newly synthesized genomes are transported to assembly sites within the cell. Capsid proteins self-assemble around the genome through specific protein-protein and protein-nucleic acid interactions. For enveloped viruses, nucleocapsids bud through cellular membranes, acquiring the envelope and glycoproteins.

Step 6: Release

Non-enveloped viruses (e.g., poliovirus) cause cell rupture (lysis), releasing progeny virions and killing the host cell. Enveloped viruses (e.g., influenza, HIV) exit by budding from the plasma membrane, often without immediately killing the cell. Some viruses (e.g., herpesviruses, HIV) can spread through syncytia formation or cell junctions (direct cell-to-cell spread), evading immune detection.

Latency and Persistence

Some viruses, such as herpes simplex and HIV, establish latent infections where the viral genome persists in cells without active replication, and reactivation can occur under immunosuppression or stress.