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Title: Viral Pathology - Influenza, HIV, Epstein-Barr and Herpes
Description: Summary of pathology and molecular biology of four viruses: Influenza, HIV, EB and Herpes. Notes taken from third year biology pathophysiology unit.
Description: Summary of pathology and molecular biology of four viruses: Influenza, HIV, EB and Herpes. Notes taken from third year biology pathophysiology unit.
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Viral Pathologies
Influenza (Orthomyxoviridae)
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Three categories, cat A with variants of Haemagglutinin (H) and Neuraminidase (N)
– 16 variants of H and 9 variants of N
Transmission by breathing in nuclei droplets
Pathogenesis
o Initial upper airway infection – kills mucus secreting epithelial cells, allowing
extracellular fluid to escape (runny nose)
o Spread to lower respiratory tract – shedding of alveolar and bronchial cells,
promoting bacterial adhesion
Treatments
o Spread to lower respiratory tract can be reduced by rest
o Keeping warm (37°C or more) – inhibits viral replication which is optimal at
35°C
o Zanamivir and Oseltamivir – antiviral drugs which inhibit Neuraminidase –
required for replication and release
Life cycle
o Neuraminidase binds to sailic acid, a component of epithelial glycoproteins,
resulting in endocytosis of the virus by host cell
o The virus is targeted to the endosome for degradation, but the acid
environment in the endosome activates capsid disassembly
o Ribonuclearproteins (RNPs) hijack cellular machinery, degrading cellular RNA
to use for viral genome replication, resulting in cell death
o Golgi complex used to make proteins, and then the virus buds off the
infected cells for release and reinfection
Herpes
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Herpes simplex 1 – cold sore
Herpes simplex 2 – genital herpes
Infects neurons
72 genes – long unique region (56 genes), short unique region (12 genes)
Five proteins from long unique region form the viral capsid – UL 6 , UL 18 , UL 35 , UL 38 ,
UL 19
Three phases of gene expression
o Tegument proteins regulate production of mRNAs and proteins of IE
immediate early genes, which protect the virus against innate host immunity
and promote transcription of early genes
o Production of E early mRNAs and proteins, which are involved in viral
replication
o Production of L late mRNAs and proteins which are involved in viral assembly
Epstein - Barr virus
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The cause of infectious mononucleosis (IM) also known as glandular fever
EBV also known as human herpes type 4
Infects B cells
Associated with cancers and neurodegenerative diseases
85 genes
Lytic EBV – acute, linear dsDNA
Latent EBV – genome inactive, circular dsDNA form
Herpes and EB viruses
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Structure – envelope and capsid, 120-200nm
Viral genome – DNA genome, double stranded, 120-240 kb, linear in acute, circular
in latent phase
Regulation of host immunity – can down-regulate pro-inflammatory responses and
MHC-II complex in infected cells
Can infect B and T cells
Widespread human infection – herpes >60%, cytomegalovirus >90%
Entry and exit
o Capsid assembly in nucleus
o Passage through nuclear membrane
o Exit from ER loosing the membrane
o Passage through Golgi complex, acquiring two membranes
o Exit through plasma membrane, losing one of the membranes originating
from host Golgi
Finds suitable host cell by recognition of heparin sulphate proteoglycan, fusion with
cell membrane
Immune evasion
o Transport associated protein (TAP) usually transports digested viral epitopes
to the ER for combination with MHC Class I
o MHC Class I presentation inactivates cytotoxic T-lymphocytes
o HSV interferes with MHC Class I antigen presentation, blocking TAP by the
secretion of ICP- 47
HIV and viral genome morphology
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Virus genome – ssRNA+ genome, 2n, same sense as mRNA
Virus morphology – protein capsid and envelope
Total size of genome – 9700 nt
Important genes
o Gag – encodes capsid proteins
o Env - encodes envelope proteins
o Pol – encodes reverse transcriptase and integrase
Reverse transcriptase catalyses:
o RNA dependent DNA synthesis
o RNA degradation
o DNA dependent DNA synthesis
HIV genome integrated into host genome – requires integrase
HIV regulatory proteins
o Gag (capsid), Pol (polymerase) and Env (envelope)
o Vif, Vpr and Vpu are regulatory proteins with various functions
o Rev regulates nuclear export of the RNA
o Nef interferes with protein trafficking
o Tat regulates transcription
RNA is spliced, Rev, Tat and Nef are translated first
Mature RNA must not be spliced
o Rev enters the nucleus
o Binds to the rev response element (RRE)
o Rev protects RNA from splicing
Title: Viral Pathology - Influenza, HIV, Epstein-Barr and Herpes
Description: Summary of pathology and molecular biology of four viruses: Influenza, HIV, EB and Herpes. Notes taken from third year biology pathophysiology unit.
Description: Summary of pathology and molecular biology of four viruses: Influenza, HIV, EB and Herpes. Notes taken from third year biology pathophysiology unit.