L26 - Herpes Simplex Virus Flashcards
What are the characteristics of the herpesvirus family? Genome? Size?
- DdDNA gnome virus
- envelope derived from original infection
- DsDNA linear genome protected by capsid
- Less ordered proteins that carries it with
- Lycoprotein spikes (several functions including binding to target cell)
How big are they
- upper range of virus size depending on its diameter and genome size
How are herpesvirus categorised?
3 diff subgroups according to host range, genetic organisation and replication strategy
Neurons - a
Myeloid cells - b
Lymphocytes - y
Why is herpes considered a low profile disease?
All humans are infected with a herpevirus
- picked up and it stays for the rest of our life
- Low profile bc it’s rarely severe
What is HSV1 and its main characteristics
- 2/3 of the human population has it
- infections are asymptomatic
- recurrent cold sores
What are the 2 important anatomical sites of HSV1 infections
Mucosa - primary infection/reaci vacation
Peripheral nervous system - lifelong latent infection
What is the transmission anad primary productive infection of HSV1
- acquire by oral to oral, oral to genital, genital to oral
- Intimate physical touch to through droplets
- Moves through barrier and binds to epithelial cell and enters
- First stages = wants to replicate
Describe the stages of cellular entry ad replication of HSV1
Replication occurs in nucleus
- binds via surface glycoproteins
- Membrane lipid envelop fuses with plasma membrane e
- Delivers capsid to teh cell
- Capsid delivered to cytoplasm and transported from membrane to nuclear pore
- Linear dsDNA replicates in nucleus
- It circularises and it begins to express genes
Which innate immune system am 1? A system of circulating and membrane bound proteins activated b y microbe bound Ab. Mannose binding lectin or the microbial surface it can promote inflammation opsonise microorganisms and directly lyse bacteria
Complement
What happens during innate immune sensing primary infection
- multiple PPRs recognised by multiple receptors
- cells detects and upregulates the type 1 interferon production
- IFN a/b induces antiviral state in surrounding cells
Describe the innate immune control of HSV infection
NK cells directly kill HSV-infected cells early in infection. Dendritic cells detect HSV and activate the adaptive immune response through cross-presentation, allowing CD4+ and CD8+ T cells to respond to exogenous viral antigens. Inflammation from the infection also triggers cytokine production, enhancing antiviral defense and recruiting more immune cells.
How is HSV a latent infection
After infecting epithelial cells, the virus is released and binds to nerve terminals. The viral capsid is transported along the axon to the nucleus, where the genome is delivered and latency is established—allowing viral DNA to persist without active replication. The nervous system is an ideal site because the immune system avoids damaging it. Therefore, the body uses non-destructive mechanisms (e.g., CD8+ T cell surveillance without inflammation) to control the virus, enabling lifelong infection without tissue damage.
How is HSV reactivated?
Stress such as UV, fever, nd fatigue triggers reaactivation and viral replication and new virisons are transcribed
Describe how reactivación can lead to infectious blinding
- infectious particles within te eye
- Reccurent activation in optic regions (scaring and multiple rounds of inflammation)
In terms of adaptive immunity herpes simplex 1 is an immune competent host and balance between what is established
Asymptomatic latency and periodic activation
What is the primary immune response for herpes simp0lex 1
- dendritic cell activates CD4 and CD8
- Activated to become antiviral
- Produces cytokines
- Activates macrophages
- Primar: activation of B cells & plasma cells and antibodies
- All these activation = memory cells
How do we know adaptive immmunity is important
- mouse model - taken to CD4 (injecting antibody which coats to CD4 T cells and recognised by NK cells which lyses teh CD4)
- Virus drops from 1-6 days
- Levels of infection remains high in the mouse without CD4
How does herpes simplex 1 modulate the adaptive immunity
Viruses can suppress type I interferon responses using viral gene products, weakening early antiviral defenses. They also interfere with antigen presentation by inhibiting the transporter associated with antigen processing (TAP), blocking peptide delivery to the ER. This prevents viral peptides from loading onto MHC class I, so infected cells are not recognized by CD8+ T cells—allowing the virus to evade immune detection even during active gene expression.
ICP47 prevents transport of viral peptides into the ER.
Empty MHCI molecules presented at cell surface.
CD8 cytotoxic T cells cannot recognize infected cells.
