38 Lentiviruses + HIV

Question 1

HIV structure

Answer 1

single stranded
+ sense
enveloped
icosahedral

Question 2

Endogenous retroviruses

Answer 2

transmitter vertically
no virions
human placental virus

Question 3

Exogenous retroviruses

Answer 3

Spumavirinae: human foamy virus; not associated with human disease, not pathogenic, seen in diseased individuals
Oncovirinae: human t-cell lymphotropic virus-bovine leukemia virus group; immortalize/transform target cells
Lentivirinae: HIV1/2, 1 = more virulent, infective, widespread

Question 4

Virus structure

Answer 4

Enveloped spherical/icosahedral

Parts: envelope, lipid membrane, matrix protein, core (inside capsid, 2 ssRNA)

Question 5

Envelope

Answer 5

glycosylated outer surface w/ envelope glycoprotein spikes

Full length protein: gp160
Surface protein: gp120; determines tissue tropism; five variable regions (mutates for protection); binds to CD4 and co-receptors of host cell
Transmembrane protein: gp41; promotes cell to cell fusion

Outer matrix protein: p17; below lipid membrane, directs entry of DNA to nucleus

Question 6

Core

Answer 6

Inside capsid

Major capsid protein: p24; specific for HIV;
Genome: + sense ssRNA, basic nucleocapsid protein (p7, p9, for infectivity)

Question 7

Enzymes in the capsid

Answer 7

Reverse transcriptase (RT) (most important)
Integrase (IN): integrates viral DNA into host
Protease (PR): cleaves viral polypeptide into functional proteins
Ribonuclease: degrade RNA

Question 8

Genome

Answer 8

Nine genes

Oncogenic: 3 genes
Simple retroviruses (HTLV): gag, pol, env
Complex retroviruses: accessory genes + gag, pol, env

Question 9

Genes for structural proteins and enzymes

Answer 9

Gag gene (group specific antigen gene)
p17: outer protein matrix (MA)
p24: capsid (CA)
p7/p9: nucleocapsid (NC)

Pol (polymerase gene): viral enzymes (RT, IN, PR, ribonuclease)
Env gene (envelope glycoprotein)
gp160 -> gp120 (SU) gp41 (TM)

Question 10

Genes for regulatory proteins

Answer 10

Tat gene (transactivator): early phase replication proteins; initiates transcription, prevents premature termination
Rev gene (regulator of viral gene expression): late phase replication; RNA splicing and export

Question 11

Genes for accessory proteins

Answer 11

Nef gene (negative regulatory factor): t-cell activation + persistent infection; increases viral infectivity;
Vif gene (virion infectivity factor): assembly and replication
Vpr/Vpx gene (viral protein r/x): regulates nuclear import, arrests cell growth
Vpu gene: virion assembly and release, degradation of CD4

Question 12

HIV cellular targets

Answer 12

SU/gp120 binds to:
CD4 receptors (t helper cells, monocytes, macrophages, DCs)
Co-receptors: CCR5/CXCR4 permits virion entry

M tropic = target macrophage
T tropic = T cell

Question 13

Macrophage as cellular target

Answer 13

Co-receptor: CCR5
early stage target (first line)
very mobile
major reservoir for hiv (easy spreading)

Question 14

T-lymph as cellular target

Answer 14

Co-receptor: CXCR4

depletes T cells (bursts from viral production)

Question 15

(life cycle) attachment/binding

Answer 15

virion attaches to host cell surface receptor

gp120 attaches to CD4 receptor

Question 16

(life cycle) penetration/fusion

Answer 16

binding to CD4 via gp120 + coreceptor -> change in gp120 -> gp41 promotes cell fusion -> viral nucleocapsid enters host cell -> release contents into cytoplasm

Question 17

(life cycle) reverse transcription

Answer 17

reverse transcriptase synthesize DNA/RNA hybrid -> ribonuclease degrades parental RNA in hybrid -> polymerase synthesize DNA -> provirus (dsDNA)

occurs in cytoplasm
no proofreading capacity

Question 18

(life cycle) integration

Answer 18

p17 transport provirus into nucleus

Integrase: cleaves host DNA and insert provirus via covalent bond

Question 19

(life cycle) transcription and translation

Answer 19

transcription of new viral RNA: activation -> transcription of provirus DNA
translation of viral building blocks

Question 20

(life cycle) assembly

Answer 20

2 new viral RNA strands and replication enzymes
core proteins = capsid
immature HIV

Question 21

(life cycle) budding and maturation

Answer 21

Budding: host derived envelope (pinocytosis)
Maturation: protease cleaves polyproteins and activates (final morphogenesis of gag-pol into gag + pol polypeptides)

Question 22

outstanding characteristics of hiv

Answer 22

non-oncogenic and cytocidal
infect immune cells
permanent association of proviruses
cause slowly progressive chronic diseases

Question 23

modes of transmission

Answer 23

sexual contact
perinatal transmission
contaminated needles
blood transfusion

Question 24

(pathogenesis) primary infection

Answer 24

transient (acute phase) viremia: upsurge of viral RNA copies in plasma within several weeks
CD4 count drops

flu-like/non-specific symptoms

Question 25

(pathogenesis) seroconversion

Answer 25

low CD4 -> high CD4 (6-8 w)
drop of viral RNA and upsurge of CD4
HIV antibodies develop, fighting infection

body tries to recover

Question 26

(pathogenesis) clinical latency

Answer 26

after 9-12 w, up to 8-10 y
continuing rate of virus production and t cell destruction
CD4 count is same level or littler difference

don’t know you’re affected

Question 27

(pathogenesis) aids

Answer 27

CD4 <200 cells/uL
HIV titers increase (body recognizes infection)
seeding in many compartments of the body

full blown infection
death: close to none CD4 levels, fast progression of any infection

Question 28

diagnostic criteria

Answer 28

+ HIV
CD4 < 200 cells/uL
CD4 <15% of baseline
diagnosis of aids-defining illnesses

Question 29

lab diagnosis

Answer 29

virus isolation
serology (ELISA, western blot)
nucleic acid testing (direct, rt-pcr, dna-pcr, bDNA)
plasma viral load
absolute CD4 count and CD4:CD8 t cell ratio
4th gen HIV test: tests for p24/capsid