Virology: Viral Families, Replication Mechanisms, and Pathogenesis

Hemagglutinin (HA)

Influenza attachment protein; binds sialic acid

HA0

Uncleaved HA precursor; must be cut by a cellular protease for infectivity

Neuraminidase (NA)

Cleaves sialic acid so progeny virions can leave the cell

M1

Influenza matrix protein; must release the RNPs during uncoating

M2

Influenza A ion channel; acidifies the endosome to release the RNPs

NP

Influenza nucleoprotein; coats the genome segments

NS1

Blocks nuclear export of cellular pre-mRNAs, keeping cap donors available

PB1

Influenza polymerase subunit; performs chain elongation

PB2

Influenza polymerase subunit; binds the host 5' cap

PA

Influenza polymerase subunit; endonuclease that cuts the stolen cap

Cap snatching

Cutting a 5' cap from a host pre-mRNA to prime viral transcription

Antigenic drift

Point mutations in HA and NA; gradual; causes seasonal epidemics

Antigenic shift

Reassortment of whole segments; abrupt; causes pandemics

Oseltamivir

Neuraminidase inhibitor

Amantadine

M2 ion channel blocker; influenza A only

NB

Protein unique to influenza B

HEF

Protein unique to influenza C

VP16

Tegument protein that transactivates the alpha (immediate-early) genes

VHS

Tegument protein that degrades host mRNA (virion host shutoff)

ICP8

Binds single-stranded DNA and prevents it reannealing

UL9

Binds the viral origin of replication and unwinds the DNA

UL30

The herpesvirus DNA-dependent DNA polymerase

Thymidine kinase

Phosphorylates acyclovir about 200x better than the host enzyme

LATs

The only transcripts made during neuronal latency

Glycoprotein D (gD)

Binds nectin-1 or HVEM and triggers fusion

Glycoproteins B and C

Herpesvirus attachment to heparan sulfate proteoglycan

Tegument

Protein layer between the herpesvirus capsid and envelope

Alpha genes

Herpes immediate-early class; regulatory proteins that switch on beta

Beta genes

Herpes early class; the replication machinery

Gamma genes

Herpes late class; structural proteins

Episome

Circular non-integrated genome form; how herpes persists in latency

Concatemer

Head-to-tail array of genomes from rolling-circle replication

Acyclovir

Activated by viral thymidine kinase, then inhibits the viral DNA polymerase

Ribonucleotide reductase

Herpes enzyme that enlarges the nucleotide pool

gp120

HIV surface protein; binds CD4 and the chemokine co-receptor

gp41

HIV transmembrane protein; anchors gp120 and drives fusion

gp160

Envelope precursor cut into gp120 and gp41 by a HOST Golgi protease

p24

HIV cone-shaped capsid protein surrounding the two genome copies

p17

HIV matrix protein lining the inside of the envelope

Reverse transcriptase

Makes dsDNA from the RNA genome; also has RNase H activity

Integrase

Inserts the proviral DNA into a host chromosome

HIV protease

Cuts the Gag and Gag-Pol polyproteins into mature proteins

Tat

Binds TAR on its own transcript and greatly increases transcription

Rev

Shuttles unspliced and singly spliced transcripts out of the nucleus

Nef

Downregulates CD4 and MHC class I so infected cells evade killer T cells

Vpu

Degrades CD4 and assists virion release

U3

LTR element containing the promoter and enhancer

R

LTR element repeated at both ends of the RNA genome

U5

LTR element unique to the 5' end of the RNA genome

LTR

U3-R-U5; complete repeat at both ends of the provirus

gag

Encodes the structural core proteins: matrix, capsid, nucleocapsid

pol

Encodes reverse transcriptase, integrase and protease

env

Encodes gp160, the envelope precursor

Slippery sequence

Site of the minus-1 ribosomal frameshift that makes Gag-Pol

Provirus

Integrated double-stranded DNA form of a retroviral genome

tRNA-Lys3

Host molecule used to prime reverse transcription

N protein

Encapsidates the rhabdovirus genome; the most abundant protein made

P protein

Cofactor required for the rhabdovirus polymerase to function

M protein (rabies)

Matrix protein; drives bullet-shaped budding

G protein

Rhabdovirus attachment protein, homologous to snake neurotoxins

L protein

Rhabdovirus RdRp; also caps, methylates and polyadenylates

Negri bodies

Cytoplasmic inclusions seen in rabies-infected neurons

Transcription gradient

Polymerase falls off at intergenic junctions, so 3' genes are made most

Subgenomic mRNA

Separate monocistronic transcript; rabies makes five

A27L

Poxvirus attachment protein; interacts with glycosaminoglycans

F13L

Poxvirus envelope protein targeted by tecovirimat

E9

Poxvirus DNA-dependent DNA polymerase

ETF

Poxvirus early transcription factor packaged in the lateral bodies

Lateral bodies

Poxvirus structures housing the enzymes needed to make mRNA

Tecovirimat

Antiviral targeting the poxvirus F13L envelope protein

Early genes (pox)

Encode the factors needed to transcribe the intermediate class

Late genes (pox)

Encode structural proteins and the enzymes that get packaged

RdRp

RNA-dependent RNA polymerase

DdRp

DNA-dependent RNA polymerase

DdDp

DNA-dependent DNA polymerase

RI-1

Minus-genome template producing plus antigenomes

RI-2

Plus-antigenome template producing about 50 minus genomes

Antigenome

Full-length plus-sense copy used only as a template for new genomes

Centrifugal

Rash heaviest on the face and extremities; smallpox

Centripetal

Rash heaviest on the trunk; chickenpox

Direct fusion

Entry at the plasma membrane without endocytosis

Receptor-mediated endocytosis

Entry by uptake into an endosome

HSV-1

Cold sores and encephalitis; latent in the trigeminal ganglion

HSV-2

Genital and neonatal herpes; latent in the sacral ganglia

VZV

Chickenpox then shingles; the only airborne herpesvirus

EBV

Mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma; infects B cells

CMV

Retinitis and colitis in the immunocompromised; top congenital viral cause

HHV-8 (KSHV)

Kaposi's sarcoma and primary effusion lymphoma

HHV-6 and HHV-7

Roseola infantum

Influenza A

Segmented negative-sense RNA; the only type causing pandemics

Influenza B

Has NB protein; 8 segments; no animal reservoir so no shift

Influenza C

Has HEF protein; only 7 segments; mild disease

HIV-1

Worldwide lentivirus from SIVcpz in chimpanzees

HIV-2

Endemic to West Africa, less infectious; from SIVsm in sooty mangabeys

HTLV-1

Retrovirus causing adult T-cell leukemia; not a lentivirus

Rabies virus

Bullet-shaped lyssavirus; retrograde spread up nerves to the CNS

VSV

Vesicular stomatitis virus; the lab model rhabdovirus

Variola

Smallpox; eradicated 1980, stocks at CDC and in Russia

Vaccinia

Live attenuated virus used as the smallpox vaccine

Mpox

Zoonotic orthopoxvirus; milder than smallpox