summary with herpes virus L26 Flashcards
what are the characteristics of Herpesvirus family
dsDNA genome
enveloped virus with glycoproteins
160-230nm - around 70-230 genes
herpesvirus categorisation
based on host range, genetic organisation and replication strategies
alpha
beta
gamma
alpha herpesviruses
HSV-1 HS-2 VZV
short replication cycle
latency in sensory neurones
rapid cell lysis
broad host range
cold sore, genital lesions, chickenpox, shingles
beta herpesvirus
CMV HHV-7
long replication cycle
latency in monocytes/macrophages T cells
narrower host range
Enlarged host cells
gamma herpesvirus
EBV HHV8
latency in lymphoid tissue like b cells
can cause cellular transformation - cancer potential
more restricted in host range
HSV1
2/3 globally infected
most infections are asymptomatic or recurrent cold sores
genital herpes
HSV1 replication occurs in nucleus
- entry of visions via binding to extracellular matrix (nectin) using glycoproteins gB and gD
- uncoating where capsid delivers DNA via nuclear pore
- genome replication
- packaging
- release, buds into vescile, transport to membrane and released via exocytosis
HSV innate immune sensing
actives multiple PRRS - HSV1 glycoprotein B, the dsDNA of virus = all causing type 1 interferon production
secreted IFNA/B induces antiviral stae in surrounding cells, detected via a receptor, to trigger anti-viral gene expression, protected
how do we known IFN is important?
studies have shown this
- mouse, when IFNA/B receptors have been knocked out, all mice die after 3 days of HSV infection
- humans, defects in this result in life threatening infections, replicating more in cells from patients lacking PRR signalling molecules
innate immune control of HSV infection
NK cells kill infected cells and activate macrophages, activated by IFNA/B or down regulation of MHC 1 - secretes IFN-Y for macrophage activation and promoting inflammation
DC activate adaptive immunity, presenting DAMPS/PAMPs to CD8 T CELL OR CD4 T CELL
virus induces infected cell lysis, DAMPS detected by macrophage to promote inflammation
PAMPS detected by macrophages to promote inflammation
activated macrophage secrets IL-6 IL-1B and TNF for inflammation
infection of the nervous system HSV
virus enters axon/nerve and moves along via retrograde axonal transport in dynein motors to the nerve cell body to be a latent infection
genome circularises - episome and LAT is expressed
reactivation will occur due to UV, fever, stress, fatigue and this will kickstart viral transcription and production of virus to become a productive infection and then cause symptoms
in an immune competent host, a balance is established as:
asymptomatic latency and periodic reactivtation
CD8 and CD4 T cells
when activated become anti-viral effect cells and then can become long-lived CD8 T memory cells
B cells
when activated become either short lived plasma cells that produce Ab or long lived memory B cells in bone marrow
what happens during reactivation of HSV
innate and adaptive immunity work together to suppress virus
NK cells still do the same, same with type 1 interferon production to induce anti-viral state.
memory CD4 T cells secrete IFNY to have antiviral effect
memory CD8 T cells have rapid lysis of infected cells and secrete IFNY for anti viral effect
B cells produce Ab to neutralise virus and suppress transmission
viral modulation of the innate immunity
dampening of type 1 interferon response
virion components or virus proteins expressing during infection interfere with sensing and signalling, secretion ICP0, US3 to suppress IFN production and antiviral effects
viral modulation of adaptive immunity
inhibition of MHC1 Ag presentation
virus protein binds to transporter association with antigen presentation TAP 1 & 2
ICP47 prevents this transport of viral peptides into ER so empty MHC 1 molecules presented at cell surface so CD8 CTL cells cannot recognise infected cells BUT NK cells recognise this absence of MHC 1 and activate
