Vous êtes sur la page 1sur 34

Human immunodeficiency

virus
(HIV)
HIV is the cause of acquired
immune deficiency
syndrome (AIDS)
Characteristics of the virus

• Is a single stranded, diploid RNA, enveloped virus


of the lentivirus subfamily of retroviruses.
• The reverse transcriptase makes copies of DNA
from the viral RNA.
Characteristics of the virus

• Outer envelope contains a lipid matrix within which


specific viral glycoproteins are imbedded.
• These knob-like structures responsible for binding
to target cell.
Human immunodeficiency virus
Structural Genes

• Group Specific Antigen (Gag)- encodes


core protein (p24) & matrix protein (p17).
• Envelope (Env)- encodes gp160, cleaved
into gp120 & gp41.
• Polymerase (Pol)- encodes reverse
transcriptase, protease & integrase
enzyme.
Group Specific Antigen (Gag)

• Gag gene encodes for nucelocapsid & matrix


protein of virus.
• Neocleocapsid protein (p24) used in serological
test.
• p17 lies between protein core and envelope.
Envelope (Env)

• Envelope (Env) gene codes for envelope protein


gp160 will eventually be cleaved by proteases to
gp120 and gp41.
• The gp120 binds specifically to CD4 receptor on
host cell, mutates rapidly & results in antigenic
variation.
• Gp41 causes fusion of the virus to the cell
membrane & virus particle enters cell.
Polymerase (Pol)

• Polymerase (Pol) codes for reverse


transcriptase, protease & integrase enzyme.
• Located in the core, close to nucleic acids.
• Responsible for conversion of viral RNA into
DNA, integration of DNA into host cell DNA and
cleavage of protein precursors.
Important enzymes

• Reverse Transcriptase (RT) – converts RNA


genome into a DNA copy
• Integrase (IN) – inserts the DNA copy into
host genome
• Protease (PR) – Cuts and processes
immature HIV proteins into mature,
functioning proteins
Methods of transmission

• Sexually, presence of STD increases transmission.


• Exposure to infected blood or blood products.
• Sharing contaminated needles.
• Transplantation of infected tissues or organs.
• Mother to fetus, perinatal transmission variable,
dependent on viral load and mother’s
CD 4 count.
Methods of transmission

• HIV has been found in saliva and tears in very low


quantities from AIDS patients, but has never been
shown to result in transmission of HIV.
• Researchers at CDC and elsewhere have shown
no evidence of HIV transmission through
insects.
Pathogenesis

• First step, HIV attaches by gp120 to the CD4


antigen found on a variety of cells-
● helper T cells ● macrophages ● monocytes
● B cells ● microglial brain cells
● T cells infected later on.
Pathogenesis

• In early phase HIV infection,


viruses are M-tropic.
• Their gp120 is able to bind to
CD4 molecule and
chemokine receptors called
CCR5 found on
macrophages
Pathogenesis

• In late most of the viruses are


T-tropic,
• Having gp120 capable of
binding to CD4 and CXCR4
found on T4-lymphocytes.
Clinical findings

• Clinical features occur in three stages:


• Acute stage
• Latent stage
• Late, immunodeficiency stage
Acute symptoms

• Mononucleosis-like, cold or flu-like symptoms


may occur 2 to 4 weeks after infection.
– Fever, sore throat, Lymphadenopathy,
Rash, headache, Fatigue or
no symptoms may be present
Window period

• Antibody appears 3-4 wks after infection with HIV, before


antibody is detected the patient is serologically “false
negative” for HIV infection.
• Patient is highly infectious,
• Lab diagnosis during window period-
• P24 antigen assay
• Viral Culture
• PCR
Clinical Latency Period

• After initial viremia, a viral set point (viral load)


occurs.
• Patient is asymptomatic at this period.
• Though the patient is asymptomatic viral replication
occurs.
Late stage

• CD4 count gradually declines from its normal value


of 500-1200.
• Once CD4 count drops below 200/μl, infected
person is considered to have advanced HIV
disease & at risk for opportunistic infections
and malignancy.
AIDS

• In late stage neurological problem e.g.


dementia and neuropathy develops
– Most deaths occur with CD4 counts
below 50.
Opportunistic Infections

• Respiratory system ● Central/peripheral Nervous system


– Pneumocystis Carinii - Cytomegolavirus
Pneumonia. - Toxoplasmosis
– Tuberculosis - Cryptococcosis
– Kaposi's Sarcoma - Non Hodgkin's lymphoma
• Gastro-intestinal system - Varicella Zoster
– Cryptosporidiosis - Herpes simplex
– Candida ● Skin
– Cytomegolavirus - Herpes simple
– Isosporiasis - Kaposi's sarcoma
– Kaposi's Sarcoma - Varicella Zoster
Oral Candidiasis (thrush)
Oral Hairy Leukoplakia
Kaposi’s sarcoma (KS)

• Kaposi’s sarcoma is a rare


cancer of the blood vessels
that is associated with HIV.
It manifests as bluish-red
oval-shaped patches that
may eventually become
thickened. Lesions may
appear singly or in clusters.
Laboratory Diagnosis of HIV Infection

• Antibody detection
• Antigen detection
• Detection of viral nucleic acid
• Viral isolation
• Indirect predictors of HIV infection
Three types of tests

(i) Screening tests - ELISA and simple/rapid tests.


(ii) Confirmatory- Western Blot assay.
(iii) Nucleic acid based tests- Polymerase chain
reaction (PCR).
ELISA Test

• Antibodies detected in ELISA against: p24,


gp120, gp160 and gp41 antigen.
• ELISAs are for screening only
• False positives occur in alcoholism,
syphilis, and immunoproliferative diseases.
Other Screening Tests

• Agglutination tests: Latex particles, Gelatin


particles and
• Comb-dipstick based systems
• Dot-Blot Test: A rapid, cost-effective.
• Most have sensitivities and specificities of
99% and 98% respectively
Rapid Tests

• Advantages:
– quicker to perform
– do not require specialised equipment or trained
personnel
Western Blot

• Most popular confirmatory test.


• Antibodies to p24 and p55 appear earliest but
decrease or become undetectable.
• Antibodies to gp31, gp41, gp 120, and gp160
appear later but are present throughout
all stages of the disease.
Indirect immunofluorescence

Can be used to detect both virus and antibody to it.



Viral Load Tests

• Viral load is the quantity of HIV-RNA in the blood.


• Viral load tests measure the amount of HIV-RNA in
one milliliter of blood.
Issues in Testing

 HIV antibody testing and


counseling should always be
voluntary and confidential.