HIV & BIOCHEMICAL

CHANGES IN AIDS
BY
P.BHUVANESHWARI
TUTOR
BIOCHEMISTRY
PSPMCH & RI
 HIV
• Human Immunodeficiency Virus (HIV)- virus that
primarily infects cells of the immune system & that
causes AIDS
• AIDS- disease that is caused by HIV infection, which
weakens the immune system.
• Discovered by Luc Montagnier & Robert Gallo
(1983–84)
• Previously called HTLV‑III (Human T‑cell
lymphotropic virus)
• A lymphadenopathy‑associated virus (LAV)
• AIDS‑associated retrovirus (ARV)
Structure of HIV
Characteristics of Virus
• Icosahedral (20‑sided), enveloped virus (lentivirus
subfamily of retroviruses)
• Two viral strands of RNA found in the core,
surrounded by protein outer coat
• Outer envelope contains a lipid matrix in which
specific viral glycoproteins are embedded; knob‑like
structures are responsible for binding to target cells:
gp120, gp41
• Within the envelope there is HIV protein called p17
& within this is the viral core/capsid (p24)
HIV Genes
• There are 3 structural genes (gag, pol and env), 3 regulatory
genes (tat, rev and nef) and 5 accessory genes (vif, vpr, vpu,
vpt and tev / tnv).
• Gag  Capsid antigen (p24)
• Pol  Reverse Transcriptase (p66)
• Env  Surface antigen (gp120)
VIRUS ENTRY
• gp120 envelope protein binds to CD4 receptor
• CD4 binding alone is not sufficient for entry
• V3 loop of gp120 binds to co-receptors:
– CCR5
– CXCR4
• Triggers fusion of viral envelope with cell
membrane
• Viral core is released into host cytoplasm
Life Cycle of HIV
 Binding
 Reverse Transcription
 Integration
 Transcription
 Translation
 Assembly
 Immunology of AIDS

• CD4 (T-helper) cells decrease, leading to a

weakened immune system.
• HIV binds to CD4 cells using its gp120 protein,
enters them, and destroys them.
• Macrophages and monocytes store HIV and spread
it to organs like the brain (CNS).
• HIV infection also reduces macrophage activity.
• When T-helper cells are low (<400/cumm), the body
can't produce strong antibody responses.
• Lymphokines (immune signaling proteins like
interferon and interleukin-2) are also reduced.
• As a result, the entire immune defense is weakened,
and opportunistic infections easily enter the body.
Category Examples

Cryptococcus, Candidiasis, Histoplasmosis,

Fungal Infections
Pneumocystis jirovecii (PCP)

Mycobacterial Tuberculosis (TB), Disseminated MAC,

Infections Mycobacterium kansasii

Pneumonia, Bacteremia, Sinusitis, Skin & Soft

Bacterial Infections
Tissue Infections, Salmonellosis

Viral Infections HSV, Varicella Zoster, CMV, HHV

Toxoplasmosis, Cryptosporidiosis, Giardiasis,

Parasitic Infections
Leishmaniasis, Isosporiasis

Malignancies Lymphoma, Kaposi Sarcoma

Miscellaneous Neurological Manifestations, HIV Nephropathy

Phases
• Acute Primary Infection Syndrome
– Duration: 2–3 weeks
– Often asymptomatic (Window period)
• Asymptomatic Phase
– No symptoms, but progressive decline in CD4
count
• Symptomatic Infection (AIDS)
– Occurs when CD4 < 200 cells/mm³
– Opportunistic infections appear
Course of HIV infection. I = window period;
II = seropositive period;
III = AIDS disease. Black line is antigen in blood. Red dots indicate
antibody response.
Genetic Resistance
 About 1% of population are resistant to HIV infection.
 CCR5 and CD4 proteins together form the receptors for HIV.

 People having mutated CCR5 gene, the protein is not

displayed on the macrophage surface.

 Without the CCR5 protein to latch onto, HIV fails to invade

macrophages.

 Thus an individual with mutated CCR5 gene escapes the HIV

infection.
 Immunoselection of Virus

 In the early phase, the HIV enters macrophages through a

receptor jointly made by CD4 and CCR5 proteins on the
surface of macrophages.

 The HIV surface antigen (gp120) has a perfect fit only for this
type of receptors on the macrophage (M-tropic HIV).

 So in the early period, lymphocytes are spared.

 After a few years, the gp120 is mutated, so that dual tropic

viruses are produced.
 Immunoselection of Virus

 In the late phases of the diseases, T-tropic HIV is generated.

 By this time, all the gp120 molecules are mutated, such that
they can fit only with T lymphocyte receptors made up of
CD4 and CXCR4 proteins.

 So, the T helper lymphocytes are preferentially killed leading

to the disease manifestations.
CD4 + CCR5 CD4 + CXCR4
 TRANSMISSION
Through Body fluids Through IV Drugs use
• Blood products
• Sharing Needles
• Semen
– Without sterilization
• Vaginal fluids • Increases the chances of
• Breast Milk contracting HIV
Through Sex • Mother-to-Baby

• Intercourse (penile • Before Birth

penetration into the • During Birth
vagina) • Postpartum
• Oral – After the birth
• Anal
• Digital Sex
Lab diagnosis
HIV Diagnosis (IgG/IgM Testing)
• Enzyme Immunoassays (EIAs)
• Rapid Tests
• Western Blot
Early Diagnosis in Infants
• p24 antigen testing
Monitoring ART
• CD4 Count
• Viral Load / PCR
Test Purpose

Detects antibodies against

ELISA First serological test gp120, gp41, p24. Highly
sensitive.

Western Blot Confirmatory test (Gold Standard) Expensive but specific.

Qualitative assay for HIV-1 and

Rapid Test Quick and reliable, like EIAs.
HIV-2

CD4 Count Prognosis & therapy monitoring Normal: 500–1500 cells/mm³

Useful for early detection and

PCR Detects HIV DNA in WBCs
infants.
 What It
Test Purpose
Detects

Helps when western blot is unclear;

Early
differentiates HIV-1 & HIV-2
HIV-DNA Proviral diagnosis, even
Sensitivity / Specificity
PCR (HIV) DNA during window
95% / 97%
period

NAT (Nucleic HIV RNA Detects early Detects 200–400 copies/ml; shortens
Acid Test) (viral genes) infection window period to < 2 weeks

Monitors
Real-Time HIV RNA disease and < 5000 copies/ml = good; > 1
PCR (viral load) treatment lakh/ml = poor prognosis
response
Monitors
CD4+ T-helper immune status
Normal > 400/cumm; < 300 in AIDS;
T-helper Count cells and disease
< 200 = bad prognosis
progression
Anti-HIV drugs
Drug Class Type Examples Function
Reverse AZT (zidovudine), ddI Inhibit reverse
Transcriptase Nucleoside (didanosine), ddC (zalcitabine), transcriptase by
(RT) Analogs d4T (stavudine), 3TC blocking the 2’ & 3’
Inhibitors (lamivudine), Abacavir positions of ribose.
Inhibit reverse
Non- transcriptase by a
Delavirdine, Nevirapine,
RT Inhibitor nucleoside different
Loviride, Efavirenz
Analogs mechanism (not
nucleoside-based).
Block final
Protease Saquinavir, Ritonavir, assembly and
—
Inhibitors Indinavir, Nelfinavir packaging of HIV
particles.
Reduces viral load
Combination
Combination of RT & protease and prolongs life
Therapy —
inhibitors expectancy in HIV
(HAART)
patients.
 Prevention
• Since, the major method of transmission is through

sexual contact, avoidance of extramarital relationships will

stop the spread.
• All the blood samples should be tested for the presence

Of HIV antibodies before transfusion.

• All surgical instruments should be properly sterilized.
• Disposable syringes and needles are to be used and

destroyed immediately after use.

• Boiling for 10 minutes will inactivate the virus.
• Ordinary autoclaving at 120°C for 20 minutes is

effective to sterilize instruments and gloves.

• Blood spills can be decontaminated by washing with

1% sodium hypochlorite solution, containing 10,000

ppm chlorine.
THANK YOU