T2 - Micro - Virology 4 - Retroviruses

Front 1

what two genuses are the retroviruses we care about?

Back 1

lentiviruses (HIV) and deltaretroviruses (HTLV 1 and HTLV 2)

Front 2

talk about retrovirus genomes:

Back 2

DIPLOID VIRUSES - two identical RNA copies (+ stranded).
they are NOT complementary strands, just two copies of their original, + stranded information.

the two copies are joined together by a base pairing dimer linkage (DLS = dimer linking structure)

Front 3

retrovirus replication?

Back 3

they have to carry their own polymerase with them, not transcribed once arrived. This is weird for a + sense virus, as most of the time, they don't carry their own polymerase (just a gene for one)

reverse transcriptase = RNA dependent DNA polymerase, to make a double-stranded DNA copy.

all in the cytoplasm - then the DNA goes into the nucleus where it's incorporated into the host genome.

Front 4

talk about HTLV-1 - what does it cause? where?

Back 4

found in japan, rural areas in southeast. Causes T-cell leukemia. Aggressive malignancy

also get TSP/HAM - tropical spastic paraparesis (loss of motor function).
HTLV-associated-myleopathy. Dulenation of spinal cord motor neurons.

Front 5

what does LTR do? Gag,pro,pol? envelope? how are genes expressed?

Back 5

regulatory region - all the transcription starts there. all gene action.

gag, pol are early genes (enzymes).

envelope is intermediate structural.

regulatory first, structural genes later.

usually, genes are expressed as large structures that need to get cleaved into their functional smaller forms before packaging.

just know that there are temporally regulated genes. structural later, early = gag/pro/pol

Front 6

MMTV? what's interesting?

Back 6

mouse mammory tumor virus.

can be passed through germ line as provirus, or through breast milk

may be a HMTV (human mammary tumor virus).

Front 7

what's REV? why interesting?

Back 7

reticulo endothelial virus.

very few genes, but LTR's are retained- so you know those LTRs are super important. They transcribe their genes AND other genes - so when the retrovirus gets in, the LTR gets HOST genes transcribed, and you can get caner. LTR by itself is mitogenic and causes cancer.

Front 8

where were lentiviruses first studied?

Back 8

horses. EIAV (equine infectious anemia virus) and caev cause immune disfunction in horses.

Front 9

where did HIV come from?

Back 9

SIVcpz from chimps.

HIV2 is closer to SIV than HIV.

Front 10

what clade is most common in US? why important?

Back 10

B.

different clades demand different antiretrovirals.

Front 11

how does HIV attach? enter? death?

Back 11

Don't forget TYPE 1 FUSION PROTEIN

entry by interacting with primary receptor (CD4) using GP120, then secondary receptors (cxcr4 and ccr5).

messes with both the T cell response and the cytokine response by touching both receptors.

Then, direct fusion happens and dumping of capsid into the host. NOT ENDOSOME MEDIATED!!!

note that the GP41 region has a toxin-like part on the carboxy end. Positively charged amphipathic helix that allows entry. Lysis/apoptosis result

t-cell killing

helps giant cells that allow virus to go back and forth, all die.

Front 12

what does TAT do?

Back 12

transactivator protein - binds to viral genome and encourages transcription. also is toxic. So both Gp41 and TAT can kill cells.

Front 13

what cells can get infected?

Back 13

cd4 bearing cells.

can be T cells.
macrophages
brain microglia

and INTESTINAL CELLS!
see massive depletion of T cells in the GUT during primary infection. Real action there.

Front 14

disease course of HIV?

what kills in the US? diseases?

Back 14

within weeks, huge spike in virus and drop in CD4 cells. Then, get into a setpoint - t-cells bounce back a bit, but they steadily deplete as virus rises up.

before antiretrovirals, PCP pneumonia biggest cause of death.

Now see candida albicans in the mouth (thrush) and MAC (closely related to TB, with acid fast positiveness)

KS from HHV-8

aids lymphoma.

Front 15

HIV and malignancy? why?

Back 15

not directly cancer causing.

HIV infection ups the chance of getting several cancers.

Front 16

drugs used?

Back 16

AZT was first. Inhibits reverse transcription = chain terminator.

still used in pregnant women/newborns.

recent nucleoside analogues used in combination.

now entry inhibitors, protease inhibitors

NEW DRUG - fuzeon - peptide based drug - it's a GP41 analogue.

usually, when you bind gp41, get a confirmational change that allows the fusion peptide to get in.

if you use the analogue, no confirmational change and no entry.

Front 17

what are endogenous retroviruses?

Back 17

11% of genome is transposable elements, non-expressed junk DNA, looks like retroviruses.

only 2.5% is expressed non repeating human genes.