Micro Winter 18 Retrovirus

Front 1

whats the micro on retroviruses

1. envelope?
2. genome?
3. release

Back 1

1. enveloped, diploid + sence ssRNA
glycoproteins in envelope

2. ssRNA, RNA --> DNA by reverse transcriptase adn then integrated into host genome

3. virions released by budding from cytoplasm membrane

Front 2

what are hte 2 genra of retroviruses that infect humans

Back 2

1. Lentivirus (HIV): 2 strains, leads to neurological/immunosuppressive disease. HIV 2 is less virulent and is seen in W africa

2. ONCOVIRUS (DELTARETROVITUS) HTLV: 3 strains. infection w/1 or 2 results in immortalization/transformation of target cells

Front 3

tell me about the 2 strains of lentivirus

Back 3

1. HIV 1: world wide, prevalent, serious neuro/immunosuppression

2. HIV 2: West Africa, less severe

Front 4

we know retroviruses have envelopes, what are the glycoproteins on the HIV 1 envelope

Back 4

gp120
gp41

**these are encoded in teh env gene and bind to chemokine receptors on out host cells (CXCR4, CCR5)- allows fusion
**has a diploid ssRNA genome. has reverse transcriptase to make RNA --> DNA, this DNA enters our cells (T, macro)

Front 5

what are 3 super important HIV 1 genes

Back 5

1. gag- encodes precursor to p53/55

2. pol- encodes precursoe that is cleaved into RT, integrase, and protease

3. env: cleaved into gp120 and gp41 (the glycoproteins in the envelope of HIV1)

Front 6

gag
pol
env

Back 6

the genes in HIV 1

GAG- encodes p53/55 precursor, cleaved into p7/9/17/24/25

POL: makes reverse transcriptase, integrase nad protease

env- makes gp120 adn gp41

Front 7

whats the cellular interaction to let HIV enter our T cells/macro

how then does it replicate

Back 7

1. gp120/gp41 on HIV binds chemokine receptors to let plama membranes bins (binds CXCR4, CCR5)

2. FUSION

3. HIV RNA enters cytoplasm and is converted by reverse transcriptase (RT, pol) to DNA

4. DNA enters our nucleus adn is integrated

5. actication of T cell to make replication, HIV genome being replicated

6 make new virions

7. budding, maturation into new infectious virions

Front 8

HIV 1 develops into...

Back 8

AIDS

first: acute HIV infection, viral load increases and CD4 decreases

clinical latency/chronic phase: CD4 increase a bit and viral load decreases

early sx HIV infection

AIDS CD4<400? or 200?

Front 9

tell me about hte acute HIV 1 infection

Back 9

asx or flu like

mononuclear cells are infected with HIV, sx are result of cytokine release

there is partial control of virus BUT there is still some HIV replication going on in LN

Front 10

tell me about the clinical latency stage of HIV 1

Back 10

asx,
VARIABLE time

**persistent infection and replication of HIV in infected cells

GRADUAL decline in CD4 cells

Front 11

whats the micro on retroviruses

1. envelope?
2. genome?
3. release

Back 11

1. enveloped, diploid + sence ssRNA
glycoproteins in envelope

2. ssRNA, RNA --> DNA by reverse transcriptase adn then integrated into host genome

3. virions released by budding from cytoplasm membrane

Front 12

what are hte 2 genra of retroviruses that infect humans

Back 12

1. Lentivirus (HIV): 2 strains, leads to neurological/immunosuppressive disease. HIV 2 is less virulent and is seen in W africa

2. ONCOVIRUS (DELTARETROVITUS) HTLV: 3 strains. infection w/1 or 2 results in immortalization/transformation of target cells

Front 13

tell me about the 2 strains of lentivirus

Back 13

1. HIV 1: world wide, prevalent, serious neuro/immunosuppression

2. HIV 2: West Africa, less severe

Front 14

we know retroviruses have envelopes, what are the glycoproteins on the HIV 1 envelope

Back 14

gp120
gp41

**these are encoded in teh env gene and bind to chemokine receptors on out host cells (CXCR4, CCR5)- allows fusion
**has a diploid ssRNA genome. has reverse transcriptase to make RNA --> DNA, this DNA enters our cells (T, macro)

Front 15

what are 3 super important HIV 1 genes

Back 15

1. gag- encodes precursor to p53/55

2. pol- encodes precursoe that is cleaved into RT, integrase, and protease

3. env: cleaved into gp120 and gp41 (the glycoproteins in the envelope of HIV1)

Front 16

what stage of HIV infection is there a persistent HIV replication and decline in CD4 cells

Back 16

clinical latency

Front 17

tell me about the early sx stage of HIV 1 infection

Back 17

chronic sx bc of T cell decline

diarrhea, night sweats, opprotunistic infections

HIV induces several CPE that may kill the infected cell

infectinos are NOT AIDS defining

Front 18

alright, waht is the AIDS stage of HIV 1 infection

Back 18

MUST be HIV +, duh

CD4 T <200 or <14%CD4, AIDS defining lesions

Front 19

why is AIDS related demintia common

Back 19

the macro deliver HIV to neurons

**in AIDS the immine response is super low there is <200 CD4

Front 20

tell me about AB to gp120

Back 20

they target hte gp120 on HIV BUT AB coated ciral particles are infectious and are phago by macro. it just kind helps the aids spread. bad news

Front 21

what are some AIDS defining lesions

Back 21

1. kaposis sarcoma
2. cryptococcal meningitis
3. CMV
4. MAI
5. toxoplasmosis

**these are AIDS defining lesion, along with HIV + status they DEFINE AIDS, also defining aids is CD4 <200 or CD4 <14%

Front 22

who gets HIV 1 infections

Back 22

1. 14-24 yo
2. most common infectinos through unprotected sex
3. transfisions are rare, we screen for HIV
4. spread by needles ~10%,
5. virus is spreas sex, parental, transplacental

Front 23

A 27-year-old male presents with complaints of fever, headache, sore throat, and malaise over a week and a rash for the past two days. He admitted to having unprotected sex with other men. His last encounter was three weeks earlier. He denied prior transfusions or IVDU.
Physical exam:
T: 39.2oC, P 94, R 14, BP 136/82 mmHg
Pharynx was erythematous; cervical and axillary lymphadenopathy was present. A diffuse maculopapular rash was observed on his abdomen.
Labs: mostly normal; slight elevation in serum transaminases
What’s likely?

Back 23

CMV
EBV
HIV, HIGH index of suspicion
secondary syphalis

Front 24

how is HIV dx made

Back 24

your pt has risk factors, unprotected sex, needles, etc

rare infections in pt- kaposis sarrcoma, pneumocystis pneumonia, other opprotunistic infections

Front 25

in HIV what is ...

1. category A
2. cetagory B
3. category C

Back 25

A: acute HIV presentation, clinical latency

B: infections seen in early stages of sx HIV infection

C: AIDS defining illness, pt dx with AIDS even in CD4 >200


**if at anytime the pt is CD4 <200 or 14% its AIDS regardless of wht category of sx are present

Front 26

dx of HIV

Back 26

elisa
confirmed with WB: band at p31 or p24, band at 160/120 or gp41

Front 27

what is a normal CD4:CD8 ratio, what is it in AIDS

Back 27

CD4: Cd8 1:6

**in AIDS its lower

**T cell analysis as well as PCR viral load are done once pt is confirmed HIV w.ElISA and WB

Front 28

what are hte 7 classes of antiretrovirals used for HIV 1 tx

Back 28

1. Nucleoside RT inhibitors

2. Non nucleoside RT inhibitors

3. Protease inhibitors

4. Fusion inhibitors

5. Integrase inhibitors

6. Maturation inhibitors

7. antisence drugs:

**often used in combination, called HAART- highly active antiretroviral treatment

Front 29

what are the following used for

nucleoside RT inhibitors
non nucloside RT inhibitors
protease inhibitors
fusion inhibitors
integrase inhibitors

Back 29

HAART- HIV tx

Front 30

how is HIV controlled./prevented

Back 30

EDUCATIONL use condom, clean needles, know your sex partners

vaccines not ready yet, they dont elicit a strong enough IR

Front 31

tell me a little about oncoviruses

Back 31

second category of retrovirus (HIV1/2 is in the lentivirus genra)

HTLV- 3 strains, 1-2 lead to transformation of target cells

Front 32

tell me about the micro of the HTLV

Back 32

retrovirus (like HIV lentivirus)
NOT CYTOLYTIC like HIV, persist in host for years

Front 33

is HIV or HTLV cytolytic

Back 33

HIV, recall it binds, fuses integrates, replicated and BUDS

HTLV doesnt do this, it persists inside the host for YEARS

Front 34

tell me about the clinical of HTLV1

Back 34

asx for YEARS! can progress to Acute T cell lymphocytic leukemia after 30 year latency

**Maligannt proliforation of CD4 T cells --> lymphadenopathy, hepatosplenomegaly, popular cutaneous lesion

Front 35

what retrovirus is associated with malignant proliforation of CD4 T cells

Back 35

HTLV-1

**can --> ATLL (acute t cell lymphocytic leukemia) after like 30 year latency

**when we get the malignant transformation the asx disease progresses to hepatosplenomegaly, lymphadenopathy and papulo-nodular lesions of the skin

Front 36

what is the additional gene seen in HTLV that is NOT seen in HIV

Back 36

TAX- transactivates genes for IL2 and IL2R (needed for cell proliforation)

**HTLV virus is in blood stream like HIV and infects CD4 cells

Front 37

what does TAX do

Back 37

its seen in HTLV

1. transcriptional activation of cytokine, GF, and survival factors

2. abnormal cell cycle, repressed DNA repair

3. abnormal cell cycle inhibition of appoptosis, genomic instability

**it should make sence. HTLV 1 is associated with acite t cell lymphocytic leukemia

**the tax gene makes IL2 and IL2R that is needed for cell proliforation

Front 38

what sim uncontrolled clonal proliforation that is seen in HTLV

Back 38

production of IL2 an IL2R from TAX gene in the ABSENCE of AG

Front 39

how is HTLV transmitted

Back 39

breast milk, sex, blood

HTLV infect T cells

clonol proliforation of CD4 T cells by TAX

alterations of host genome

malignant expansion (ATL)

Front 40

where might we see more causes of HTLV

Back 40

japan
caribbean
central aftica
AA

Front 41

whats the most common way HTLV is spread in US, overall is this disease increasing or decreasing

Back 41

IVDA, blood transfusion

also canbe sexial transmission adn brest milk

overall increase!!! bad news, latent for LONG time then makes cancer

Front 42

what is the dx of HTLV

Back 42

1. HTLV AG or AB w/ELISA

2. atypical lymphs on peripheral smear

3. increases WBC

4. hx: japan, caribbean, skin lesion, neurological manifestation

Front 43

what is the tx for HTLA retrovirus

Back 43

IGNa and AZT

lymphoma chemo

EDUCATION to prevent spread

Front 44

what disease

1. infects helper T cell, mono, macro
2. infects only helper T

Back 44

HIV 1

HTLV

Front 45

what disease

is WORLD WIDE

is limited to japan, caribbean, Africa, SE US

Back 45

HIV 1

HTLV

Front 46

what is the transmission of HIV and HLTV

Back 46

BOTH are blood

Front 47

what causes and acute, latency, early and full on disease?

what about what causes acute t cell lymphocytic leukemia

Back 47

HIV

HTLV

Front 48

what is the pathogensis of

HIV

HTLV

Back 48

1. HIV- destruction of T cell, cytokine stimulation enhances HIV replication

2. incontrolled proliforation of T helper cells, transactivation of IL2 adn IL2R

Front 49

whats the dx

1. decreased T, decreased CD4:CD8. what AB is detected

2. icnreased WBC, atypical lumphs, detection of what AB

Back 49

1. HIV; detect HIV AB

2. HTLVL detect HTLV AB

Front 50

what is the tx for HIV, HTLV

Back 50

HIV: nucloside RT inhibitor, non nucleoside RT inhibitos, protease inhibitor, fusion inhibitor, integrase inhibitor, maturation inhibitor, antisense drugs

HTLV: IFNa, AZT