How did HIV enter the human population ?

HIV-1 probably from chimps (butchering)

HIV-2 - probably from sooty mangabey

reverse transcriptase, polymerase, integrase

+ssRNA 

RT

RNA-dependent DNA poly

2 copies of +RNA:  NON-INFECTIOUS

Provirus-integrates into host genome

Viral mRNA encodes struct and non-struct proteins

+RNA-->dsDNA-->RNA-->proteins

funciton of env-encoded proteins in HIV

env codes gp160, which is cleaved into 

gp120 (docking "flower-petals" protein)

and

gp41 (transmembrane protein connects to gp120

HIV genes

tat

rev

encode what?

tat: modulates gene expression

rev: nucleo-cytoplasmic shuttling

These affect many pathways

HIV lifecycle

1. Binding and fusion  to CD4+: releases RNA > cell
2. Reverse Transcription: +ssRNA-->ds HIV DNA
3. Integration: HIV DNA -> host nucleus and integrase "hides" the DNA into the host's own DNA.  Provirus may be inactive for years
4. Transcription:  host cell gets sig to become active.  then provirus uses host RNA POLY to copoy HIV genome material and mRNA
5. Assembly: HIV protease cuts the long chains of HIV protiens which assemble into new virus particles
6. Budding: buds out w/ part of cell's envelope
   

Modes of HIV Transmission

Unprotected sex

shared needles

Increased risk with other STI

HIV does NOT survive long outside of host !

HIV

PATHOGENESIS

within body

(how does it get around and infect?)

TISSUE TROPHISM FOR

T-CELLS AND MACROPHAGES

Enters during sex--> MALT, bind to CCR5/CXCR4 on dendridics/Mphage/T

lytic infection of CD4, can also pass T-T cell directly forming giant syncitial cells

persistent infec. of Mphage=resirvoir + xport thru body

T cell counts go dn

OPPORTUNISTIC INFECTIONS go up

HIV spreads cell-cell-> syncitia: avoids circ. Abodies

HIV

diagnosis tools

Anibody or Antigen testing (ELISA, W. blot)

Fluid, urine, finger-stick (need confirmation)

Rapid test (needs confirmation)

What decreased incidence of

perinatally-acquired

AIDS?

Universal testing fo pregnant women for HIV

HIV therapy

When CD4+ < 350 cells/ul

(2)  Nucleoside RT inhibitors

GOAL: GET HIV RNA LEVEL BELOW DETECTION LIMITS

Can be > 750k copies/ml

Undetected = <400  not equal to uninfected

Typical HIV progression

Typical (80%).......7-10 yrs

Rapid (5-10%) ...within 2 yrs

Non-progression (10-15%)... CD4 count stays high, viral load not detectable (lack CCR5/CXCR4??)

HIV WINDOW PERIOD

Negative HIV test (primery infec to seroconversion)

but

Viral load very high, high xmission risk !

Progression of AIDS

1. Acute infection
2. Strong anti-HIV immune defense
3. latent resirvoir
4. Loss of CD4+ and loss of immune response
5. Onset of AIDS

AIDS-related infections

LIST

1. Pneumo:s pneumo., H. influ., staph aureus, pseudomon.
2. Mycobacterium Avium, TB
3. Salmonellosis, B. henselae
4. CMV, JC virus (PML)
5. Hep (HHV-8: kaposi, HPV, PML, Kaposi
6. Candida, crypto meningitiditids
7. Non-Hodgkins L., Kaposi

Aids Related Infection:

CMV

• Dormant in healthy immune systems
• Weakened immune system
  • Retinitis -->blindness if untreated
  • Digestive tract
  • Lungs, other organs

Aids-Assoc Infection

BACILLARY ANGIOMATOSIS

Bartonella henselae

• Purplish to bright red skin patches (like Kaposi)
• Vascular proliferative disease of skin, LN, liver, spleen
• Subacute endocarditis
• Cat-scratch disease lymphadenopathy

AIDS-related infection:

Salmonellosis

AIDS-related infection

BACTERIAL PNEUMONIA

S. pneumonia, H. influenza, S. aureus, pseudomonas

• Rates ↑ 25% in HIV+
• LOBAR pneumonia (abcess)
• Diagnosis sputum, blood

AIDS - related infection

MYCOBACTERIUM AVIUM

Weakly G+

Acid-fast

Aerobic

rod

soils, SALT water

M. Avium, M. intercellare

• Salt, water, soils
• CD4 < 50
• 20-30% of AIDS+ get MAC
• NIGHT SWEATS, wt.loss, diarrhea, anemia
• Pulmonary: MAC nodule full of bacteria
• ADIS-Disseminated:  1000s of bact per ml blood
• MAC Lymphadenitis - kids

AIDS-related infection

TB

M. Tuburculosis

• Most common opportunistic infection for HIV+
• LEADING CAUSE OF DEATH FOR AIDS PATIENTS
• " Twin epidemics"   (12M people have both)
• New TB vaccine (UCLA) safer, more potent than BCG

AIDS-Related infecion

VIRAL HEP B/C

• Long-term complications: cirrhosis, LIVER CANCER

• HIV + HEP--> ↑ risk of toxicity from meds

AIDS-related infection

Herpes Simplex Virus

HSV

• ↑ risk for more severe infecion
• sores take longer to heal
  
• Systemic symptoms: 
  
  • brain damage
  • blindness
    

AIDS-related infection

Progressive Multifocal

Leukoencephalopathy

(PML)

JC VIRUS

• Only see when immuno sys damaged
• Symptoms:
  • Speech problems
  • Weakness on one side of body
  • Loss of vision in one eye
  • Numbness in one arm/leg 
• Irregular areas of granularity in brain white matter (like MS-demyelination plaques)

AIDS-related infecion

Human Papilloma Virus

(HPV)

HPV

• HIV+ --> more prone to infection and cancer
• ↑risk for cervical cancer

AIDS-related infection

Karposi's sarcoma

(HHV-8)

• Tumor of BLOOD VESSEL WALLS
• Rare in non-HIV
• Pink/red/purple lesions on SKIN, MOUTH
• Internal organs also (GIT, Lungs)
• Anti-retrovirals ↓ incidence and lesions
• ONE OF THE MOST COMMONLY-DETECTED TUMORS IN AIDS

AIDS-RELATED INFECTION

Non-Hodgkin's lymphoma

• Common in those w/immune deficienty
• Autoimmune Dz, HIV, HTLV-1, HEP C, EBV ↑RISK
• Usually begin in LN lymphocytes

AIDS-related infections

Candidiasis

• Common in HIV+
• Leukoplakia (can go "hairy")
•  Normal commensal - normally harmless

AIDS-related infection

CRYPTOCOCCAL MENINGITIS

• Fungus in BIRD/BAT/PIGEON droppings
• CNS
• No person-person spread
• CD4 < 100
• Major virulence factors
  
  • polysaccharide capsule
  • phenol oxidzse enzyme
  • Ability to grow at 37 deg. C 

AIDS-related infection

Pneumocystis jirovecii

• formerly P. carinii
• Previously thought to be a parasite
• Almost exclusive in immunocompromised
• Anti-retroviral drugs have ↓ cases of PCP
• One of the most common opportunistic infections in HIV+

AIDS-related Infections

Toxoplasmosis

"Don't throw out the cat!"....or should we????

• Potentially deadly infection : ENCEPHALITIS in AIDS+
• caused by T. gondii
• Spread by cats
  
• Humans touch mouths after changing litter
• Undercooked meat, esp. pork, lamb, venison

AIDS-related infecions

Cryptosporidiosis

• Intestinal parasite
• Found in animals
• Eat contaminated food/H2O
• CD4 < 200
• Severe, chronic diarrhea self-limited if CD4>200
• Refractory to treatment w/ low CD4 counts