World of Viruses - second half

core structural proteins of Coronaviridae

S,E,M,N

The family that contains the viruses with the largest RNA genome (25-32kb)

The family coronaviridae

Polyproteins are processed by and cleaved by (Cor)

PLP and 3CLpro

How is ORF1b translated 

via a -1 ribosomal frameshift producing a larger fusion protein, pp1ab

What do ORF1a and b encode

all the proteins required for RNA synthesis

ExoN

proof-reading enzyme first identified in an RNA virus, responsible for extremely large RNA genomes in coronavirus

gene downstream of ORF1a'/b are expressed 

via a nested set of sf mRNAs 

in coronavirus sgRNAs are transcribed by

RTC using a discontinuous mod of transcription

All sgRNAs

share the same sequence in the 3’ end with each other and the same 5’ leader sequence

ACE2

angiotensin converting enzyme 2

HR

heptad repeat 

CEACAM

carcinoembryonic antigen-related cell adhesion molecule

Cleavage by shedding enzymes releases

the soluble forms of ACE and ACE2 into the blood to function

ACE2 as a receptor for

SARS-CoV and Sars-CoV2

nsp3

Papain-like protease domains (PLP1, PLP2) responsible for cleavage of nsp 1, 2, and 3. TMD for membrane association

nsp5 

Chymotrypsin-like protease (3CLpro or Mpro) responsible for most of the cleavage of the pp1a and pp1a/b

Deletion of aa69 and 70 in NTD

may alter conformation of S trimer and receptor binding

PL

papain-like protease 

3CL

3-C like cysteine protease

Delta variant

first appearance in india, 225% as transmissible as og, 17 mutations several in spike

omicron variant

first appearance in south africa, immune evasion, 30aa changes, 3 small deletions and 1 insertion —> changes in spike 

Central government notified WHO of a novel coronavirus outbreak

December 31, 2019

WHO declares ‘a public health emergency of international concern

Jan 30, 2020

Dr. Li Wen Liang

summoned to and questioned by Wuhan Public Security Bureau, accusing him ‘making false comments on the internet’

Isolation of influenza 

Sir Andrews, Sir Laidlaw, Smith at MRC

Most common & more severe, responsible for seasonal epidemics
and all the flu pandemics occurred in history

Alphainfluenzavirus influenzae. FLUAV

Betainfluenzavirus influenzae, FLUBV

Milder disease; mainly among children, geographically limited

Current taxonomy of influenza viruses

riboviria, Orthomyxoviridae, Alphainfluenzavirus, A. influenzae

Each viral RNP enters the nucleus via

NLS on NP and replicase proteins

Function of PA 

endo-nuclease activity, cleaves capped host pre-mRNA

Function of PB1

synthesizes viral mRNA using snatched oligonucleotides as primer

M1

forms the matrix layer; the most abundant protein in virion; interacts with
NEP, involved in RNP export out of nucleus

M2

forms the ion channels in the viral envelope

Antigenic drift 

minor changes in antigens, evasion of existing immunity

Antigenic shift

major shifts in surface antigens, due to re-assortment
of genome segments in cells co-infected with different strains.
Responsible for periodic pandemics

Kawaoka and Fouchier 

doing tests with GoF research, modified H5N1 with mutations in HA and PB2 that conferred transmissibility among ferrets 

Mononegavirales families 

Paramyxoviridae
Rhabdoviridae
Filoviridae
Bornaviridae

AMPE

acute post-infectious measles encephalitis 

MIBE

measles inclusion-body encephalitis

SSPE

subacute sclerosing pan-encephalitis

Dr. Peter Piot

Receiving 2 plastic vials of blood specimen from a Belgian nun in Zaire exhibiting hemorrhagic fever
Specimen vials transported on commercial flight in a carry-on bag, one vial shattered en route - discovery of Ebola

Gary Kobinger and colleagues

worked for years on this
technology, named vaccine rVSV-ZEBOV
During the Ebola outbreak in Western Africa 2014-2016