This is an antiviral gating module, not a specific disease and not a drug target. It is the antiviral analog of the antibacterial intracellular_pathogen_persistence module: both encode a pharmacologic constraint on what therapy can achieve rather than an enzyme a drug inhibits. Disorder entries for latency-establishing viral infections reference nodes via conforms_to (e.g., "viral_latency_reservoir_persistence#Antiviral Suppression Without Eradication of the Reservoir"), and their suppressive treatments — which point at a polymerase/integrase/protease target-module node via target_mechanisms for their molecular action — are gated by this module's explanation of why that action cannot cure. Key conformance / treatment-gating target: "Antiviral Suppression Without Eradication of the Reservoir" (the node that distinguishes "an antiviral is used" from "the infection is cured" — replication inhibitors cannot clear an archived, non-replicating genome, mandating lifelong therapy and motivating the functional-cure / reservoir-elimination research frontier). Worked "suppression ≠ cure" conformers are Acquired_Immunodeficiency_Syndrome (integrated proviral reservoir in resting CD4+ T cells) and Hepatitis_B (nuclear cccDNA), to be contrasted with Hepatitis_C, which is curable because it establishes no such reservoir. See projects/ANTIVIRAL.md.
Establishment of a Latent or Archival Viral Genome
trigger
After initial infection, latency-establishing viruses deposit their genome in a stable, transcriptionally quiescent form that persists independently of active replication. The molecular form varies by virus family: HIV and other retroviruses integrate a provirus into the host chromosome of long-lived resting memory CD4+ T cells; hepatitis B converts its relaxed-circular DNA into a covalently closed circular DNA (cccDNA) episome in the hepatocyte nucleus; herpes simplex virus establishes a non-replicating latent infection in sensory neurons. In each case the archived genome is laid down early, is indistinguishable from the host's own nucleic acid to the immune system, and serves as the durable template from which infectious virus can later be regenerated. This is the trigger node of the module — the event that creates a reservoir no replication-targeting drug can reach.
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Antiviral Suppression Without Eradication of the Reservoir
Once a latent or episomal genome is established, replication-targeting antivirals can suppress active virus but cannot clear the archived reservoir.
Show evidence (4 references)
"the latent HIV reservoir is established at a very early stage of the disease, just a few days after the initial infection"
Review of the HIV reservoir establishing that the latent reservoir is laid down at a very early stage of infection, the trigger event this node represents. Evidence source is OTHER as this is a review article.
"The HIV cellular reservoir comprises cells with HIV-DNA integrated into their genome, but trancriptionally silent"
Describes the archival, transcriptionally silent integrated provirus that constitutes the HIV latent genome — the retroviral instance of this establishment node. Evidence source is OTHER as this is a review article.
"cccDNA is generated as a plasmid-like episome in the host cell nucleus"
Establishes the hepatitis B cccDNA episome formed in the hepatocyte nucleus as the archival genome instance of this node. Evidence source is OTHER as this is a review article.
+ 1 more reference
Antiviral Suppression Without Eradication of the Reservoir
intrinsic resistance
Direct-acting antivirals act on the replicating virus — the polymerase, protease, integrase, or assembly machinery engaged only during active replication. The latent reservoir is, by definition, not replicating: the integrated provirus is transcriptionally silent, the cccDNA episome is a stable template rather than a replicating intermediate, and the latent neuronal HSV genome makes no infectious particles. Consequently suppressive therapy drives plasma viremia to undetectable levels and arrests disease progression but leaves the archived genome intact, so it cannot cure the infection. This is the gating principle that distinguishes suppression from eradication and mandates indefinite (often lifelong) therapy; it is the canonical conformance / treatment-gating target of the module and the reason the "functional cure" and reservoir-elimination strategies (e.g. "shock-and-kill", cccDNA-directed agents) are an active frontier rather than standard care.
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Reactivation and Viral Rebound on Treatment Interruption
Because the archived reservoir survives suppression, stopping therapy allows the latent genome to resume replication and viremia to rebound.
Show evidence (3 references)
"HIV infection is not curable with current antiretroviral therapy (ART) because a small fraction of CD4+ T cells infected prior to ART initiation persists"
States the core gating principle — ART is not curative because a persistent latently infected reservoir survives suppression. Evidence source is OTHER as this is a review article.
"Current treatment with nucleos(t)ide analogs is effective in the suppression of viral activity but generally requires lifelong treatment. They fail to eradicate the HBV viral reservoir, called covalently closed circular DNA (cccDNA)"
The hepatitis B instance of the gating principle — nucleos(t)ide analogs suppress but fail to eradicate the cccDNA reservoir, mandating lifelong therapy. Evidence source is OTHER as this is a review article.
"Current therapies rarely achieve a cure due to the refractory nature of an intracellular viral replication intermediate termed covalently closed circular (ccc) DNA"
Confirms that the refractory cccDNA reservoir is why current hepatitis B therapy rarely cures — suppression without eradication. Evidence source is OTHER as this is a review article.
Reactivation and Viral Rebound on Treatment Interruption
adaptive escape
The persistence of a suppressed-but-not-eradicated reservoir has a direct clinical consequence: when suppressive therapy is interrupted, the archived genome exits latency and reignites productive infection. For HIV, a small fraction of the latent reservoir produces infectious virus that rekindles systemic infection within weeks of stopping ART; for hepatitis B, the stable cccDNA reactivates the virus when nucleos(t)ide analogs are withdrawn; for herpes simplex virus, the latent neuronal genome periodically reactivates to cause recurrent peripheral disease, which is why no drug eradicates the virus. This rebound is the escape consequence that closes the loop of the module and operationalizes "suppression is not cure": it is the reason therapy must be continued indefinitely and the endpoint that any curative or functional-cure strategy must abolish.
Show evidence (3 references)
"A much smaller fraction is responsible for production of low levels of infectious virus, which can rekindle infection when ART is stopped"
States the HIV rebound consequence — a fraction of the reservoir produces infectious virus that rekindles infection when ART is interrupted. Evidence source is OTHER as this is a review article.
"This stable form of viral DNA can reactivate the virus when treatment is stopped."
The hepatitis B instance of reactivation/rebound — the stable cccDNA reactivates the virus when treatment is stopped. Evidence source is OTHER as this is a review article.
"latent virus can re-enter the replication cycle by reactivation and return to peripheral tissues to start recurrent infection"
Confirms the herpes simplex virus instance of reactivation — the latent neuronal genome re-enters replication to cause recurrent infection. Evidence source is OTHER as this is a review article.