B7: chronic and latent infection Flashcards
: How Do Acute and Chronic Infections Differ?
Acute infections are nonequilibrium processes resolved by either clearance or host death; chronic infections reach a metastable equilibrium where the virus persists despite the immune response.
How Is Latency Maintained in a Chronic Infection?
The virus expresses only genes needed to maintain latency (often undetectable by B and T cells) and can periodically reactivate to produce virions.
What Are Viral Strategies for Establishing Long-Term Infections?
Immune avoidance (via mutation or targeting immune-privileged sites), downregulation of antigen presentation, and manipulation of host immune responses.
How Do Viruses Generate Variants to Evade Immunity?
They accumulate mutations to avoid antibody recognition and MHC surveillance, potentially altering cell tropism.
What Immune Downregulation Strategies Do Viruses Use?
They can block T cell or NK cell function, downregulate MHC expression, produce cytokine agonists/antagonists, and interfere with interferon (IFN) pathways.
ow Does Apoptosis Inhibition Benefit Viral Infections?
By preventing premature death of the host cell, viruses can maintain a stable environment for replication during the acute phase.
What Happens to T Cells During Chronic Viral Infections?
T cells may become overactivated, exhaust, and eventually undergo terminal differentiation and death, leading to a loss of specific antiviral responses.
Is HIV an Example of a Latent or Chronic Infection?
HIV is considered a chronic infection because, despite establishing latent reservoirs, it continuously replicates at low levels and causes progressive immune system decline.
Why Is HBV Considered a Chronic Infection?
HBV maintains long-term replication with active production of viral particles, and while it can sometimes be cleared, many individuals develop a persistent infection.
What Is the Structure of HBV?
HBV is an enveloped virus with a partially double-stranded DNA genome. The surface is coated with HBsAg, and the inner capsid is made of HBcAg. The mature infectious particle is known as the Dane particle.
What Genes Does HBV Encode?
HBV encodes four open reading frames (ORFs):
ORF S: HBsAg (small, medium, large proteins)
ORF Core: HBcAg (core antigen) and HBeAg (secreted core-related protein)
ORF P: Polymerase
ORF X: HBx protein
How Is HBV Transcribed?
Transcription is mediated by RNA polymerase II using promoters (core, pre-S1, pre-S2/S, X) and enhancers (ENH1 and ENH2); an encapsidation signal is also present.
How Does HBV Attach and Enter Hepatocytes?
HBV binds to the NTCP (sodium taurocholate co-transporting peptide) receptor via HBsAg, triggering endocytosis and release of the nucleocapsid into the cytoplasm.
What Happens Once HBV’s Nucleocapsid Enters the Nucleus?
The relaxed circular DNA (rc-DNA) is released and converted to covalently closed circular DNA (cccDNA), which acts as an episomal template for transcription.
How Is the HBV Genome Replicated?
Pre-genomic RNA is produced from cccDNA, associates with core proteins, and is reverse transcribed back into rc-DNA.
What Are the Fates of the Mature HBV Core Particle?
It can either recycle back to the nucleus to replenish cccDNA or associate with HBsAg in the endoplasmic reticulum for virion assembly.
What HBV Serological Markers Indicate Infection or Recovery?
HBsAg: Presence indicates infection (acute or chronic).
Anti-HBs: Indicates recovery and immunity.
Anti-HBc: Indicates previous or ongoing infection; IgM anti-HBc appears during acute infection.
What Are the General Features of Herpes Viruses?
Herpes viruses are icosahedral, enveloped, double-stranded DNA viruses with a tegument layer; they establish lifelong infections.
How Are Human Herpes Viruses Classified by Target and Latency?
Alpha herpesviruses (e.g., HSV-1, HSV-2) target epithelia and are neurotropic.
Beta and Gamma herpesviruses target lymphocytes and are lymphotropic.
What Is the Typical Presentation of HSV-1 and HSV-2?
HSV-1 usually causes oral lesions (cold sores, herpes keratitis) above the waist, while HSV-2 causes genital herpes below the waist.
What Is Gingivostomatitis?
The initial presentation of HSV infection in the oral cavity, often seen during primary infection.
How Does HSV Replicate Upon Initial Infection?
HSV binds to heparan sulfate via glycoproteins (gB, gC, and gH/gL), then interacts with the receptor nectin-1 via gD, leading to membrane fusion and entry of the capsid into the cell.
Describe HSV Capsid Entry and Genome Transport.
After membrane fusion, the capsid travels to the nucleus where the linear double-stranded DNA is released for replication.
What Characterizes HSV Latency?
During latency, there is minimal gene expression—limited primarily to the production of latency-associated (Lat) RNA—with no productive viral replication.
How Does HSV Reactivate?
Reactivation leads to new capsid formation in the nucleus, which then buds through the nuclear membrane, is transported along axons, and results in secondary infection.
What Strategies Do Viruses Use to Evade the Immune System in Chronic Infections?
They may use immune avoidance tactics such as targeting immune-privileged sites (e.g., eye, CNS, skin), downregulating antigen presentation, or generating variants by mutation.
How Do Viruses Downregulate Host Immunity?
By expressing viral genes that block T cell or NK cell functions, decrease MHC molecule presentation, and interfere with cytokine (especially IFN) signalling pathways.
