Proviruses

A provirus is a viral genome that has integrated permanently into a host cell’s genome. The term is most often used for retroviruses, which replicate via a DNA intermediate. After entry, the viral RNA genome is reverse-transcribed into complementary DNA (cDNA) by reverse transcriptase, and the cDNA is integrated into the host genome by the viral integrase enzyme. Once integrated, the viral sequence is referred to as a provirus and is replicated with the host DNA during cell division. The provirus may remain transcriptionally silent (latent) or be actively transcribed, depending on the chromatin state and cellular environment. When transcribed, viral RNAs serve as genomes for new virions and as mRNAs for viral proteins; new virions are produced and can infect other cells.

For bacteriophages, a related concept is the prophage, the integrated form of a phage genome in a bacterial host during lysogeny.

Endogenous retroviruses are proviruses that have become fixed in the germ line and are inherited across generations. Most ERVs are defective, but some have been co-opted by the host for beneficial functions, such as placental development in some mammals.

Clinical and research relevance: proviral integration can disrupt host genes or alter regulation, contributing to disease in some cases; retroviral vectors exploit proviral integration for gene delivery, but pose risks of insertional mutagenesis. Antiretroviral therapies target steps of proviral replication, such as reverse transcription and integration (e.g., integrase inhibitors).