Human Immunodeficiency Virus Dr. Suhail Naser. Human Immunodeficiency Virus (HIV) is the causative...
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Transcript of Human Immunodeficiency Virus Dr. Suhail Naser. Human Immunodeficiency Virus (HIV) is the causative...
Human Immunodeficiency Virus
Dr. Suhail Naser
Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immune Deficiency Syndrome (AIDS).
HIV-2 was isolated in 1986 in West Africa
HIV-1 was isolated in 1983 in France and USA
Human Immunodeficiency Virus•Belong to the lentivirus subfamily of the retroviridae
•Enveloped RNA virus, 120nm in diameter
•HIV-2 shares 40% nucleotide homology with HIV-1
•Genome consists of 9200 nucleotides (HIV-1):
•gag core proteins - p15, p17 and p24
•pol - p16 (protease), p31 (integrase/endonuclease)
•env - gp160 (gp120:outer membrane part, gp41: transmembrane part)
•Other regulatory genes ie. tat, rev, vif, nef, vpr and vpu
STRUCTURE OF HIV
HIV particles
HIV Genes
• Three basic genes– gag – encodes matrix, capsid, nucleic acid
binding proteins– pol – encodes reverse transcriptase– env - encodes surface glycoproteins,
transmembrane proteins
HIV Antigens
• Major surface/envelope glycoproteins– gp120– gp41 anchors gp120 to virus
• Major capsid proteins– p24– P18
• Other minor surface & structural proteins– p55
Replication
• The first step of infection is the binding of gp120 to the CD4 receptor of the cell, which is followed by penetration and uncoating.
• The RNA genome is then reverse transcribed into a DNA provirus which is integrated into the cell genome.
• This is followed by the synthesis and maturation of virus progeny.
CO-RECEPTORS
• HIV infects and ultimately destroys CD4+ ,CCR5+ or CXCR4+ are the co-receptors necessary for attachment.
Schematic of HIV Replication
CELLS WHICH ARE INFECTED BY HIV
All cells which have CD4 receptors on their surface.
• T4 (Helper/inducer) lymphocytes
• 5-10% B lymphocytes.
• 10-20% Monocytes & Macrophages.
• Glial cells and microglia in CNS.
MODE OF TRANSMISSION OF HIV
•Sexual contact
•Intravenous drug use
•Transfusion of blood and infusion of blood products
•Mother to foetus-Perinatal
•Others
MODES OF ACCQUIRING HIV.• Sexual Contact = 0.1 -1.0 %• Transfusion of blood and blood products = > 90%• Tissues and organ donation = 50 -90%• Injections and injuries, unsterile needles = 0.5 -1.0%• Mother to baby (transplacental) = 30%• SECRETIONS WHICH HAVE HIV • Blood• Lymphocytes.• Semen • Saliva• Urine • Tears• Breast milk.
Others (not specified)
Injectable Drug use
Blood and blood products
Perinatal
Sexual
85.7 %
6.8 %
2.2 %2.6 %
2.7
MODES OF SPREAD OF HIV
• HIV infects and destroys an important type of cell in the body’s immune system known as the T-helper (TH) cell, also known as the CD4 cell
How does HIV cause AIDS?
• CD4 cells direct and coordinate other cells in the immune system to battle infections
• When CD4 cells are destroyed, the body loses its ability to fight off infections
How does HIV cause AIDS?
CD4 Cells
4-8 Weeks Up to 12 Years 2-3 Years
CD
4 Cell C
ount
1,000
500
Asymptomatic HIV Infection AIDS
Acute Infection
HIV Infection is characterized by a steady decline in the number of CD4
cells
Time
200
CD4 cell count
4-8 Weeks Up to 12 Years 2-3 Years
CD
4 C
ell C
oun
t (c
ells
/mm
³)
1,000
500
Asymptomatic HIV Infection AIDS
Acute Infection
HIV Infection is characterized by a steady decline in the number of CD4
cells
Time
200
high risk of opportunistic infections
Clinical Features
1. Seroconversion illness - seen in 10% of individuals a few weeks after exposure and coincides with seroconversion. Presents with an infectious mononucleosis like illness.
2. Incubation period - this is the period when the patient is completely asymptomatic and may vary from a few months to a more than 10 years. The median incubation period is 8-10 years.
3. AIDS-(CD 4 Count less than 200/cc)related complex or persistent generalized lymphadenopathy.
4. Full-blown AIDS.
Opportunistic Infections
Protozoal pneumocystis carinii (now thought to be a fungi),
toxoplasmosis, crytosporidosis
Fungal candidiasis, crytococcosis
histoplasmosis, coccidiodomycosis
Bacterial Mycobacterium avium complex, MTB
atypical mycobacterial disease
salmonella septicaemia
multiple or recurrent pyogenic bacterial infection
Viral Cytomegalovirus, HerpesSimplexVirus,
Varicella Zoster Virus, JCV
Opportunistic Tumours
• The most frequent opportunistic tumour, Kaposi's sarcoma, is observed in 20% of patients with AIDS.
• KS is observed mostly in homosexuals and its relative incidence is declining. It is now associated with a human herpes virus 8 (HHV-8).
• Malignant lymphomas are also frequently seen in AIDS patients.
What is the “Viral Load”?
• The HIV viral load is simply a measure of the quantity of HIV in a drop (mL) of a patient’s blood, and it is usually measured in copies/mL
• In general, the higher the viral load, the faster CD4 cells are destroyed
Laboratory Diagnosis
Test Serology
ELISA Latex Agglutination Western Blot Immunofluorescence
Virion RNA, RT-PCR P24 antigen Isolation of virus
Lymphocyte CD4:CD8 T cell ratio
Objective
Initial ScreeningInitial ScreeningConfirmatory testConfirmatory test
Detection of virus in bloodEarly marker of infectionTest not readily available
Correlate of HIV Disease
SPECIMENS FOR DIAGNOSIS OF HIV INFECTION
SerumVenous blood drawn using syringes and collection tubes (e.g. vacutainers), and serum separated from blood by centrifugation
Most common testing media for all kinds of tests
•Time consuming•Staff with a higher level of training required•Costly•Risk of occupational exposure
Whole Blood from finger prick •easy to perform, •require minimal equipment•can be carried out by the appropriately trained counsellor•Less costly•risk of occupational exposure is substantially reduced
SPECIMENS FOR DIAGNOSIS OF HIV INFECTION
Saliva and Urine
•Collection-simple, safe, non-invasive, inexpensive, and the sample can be stored at room temperature
•Can be collected in groups•Safer to collect than blood (less infectious)•Eliminates the risk of accidental exposure through needle stick or test tube breakage
•Can be collected from persons unwilling to giving blood•Useful for testing hard-to-reach populations such as sex workers and at sites where blood collection may be difficult, such as remote clinics or point-of-care facilities.
•Cost-effective-minimal training, no equipment for collection
However, the quality of these assays as compared to conventional serological tests needs to be assessed
Laboratory tests for diagnosis of HIV infection
Screening tests
Supplemental tests
Confirmatory tests
ELISA Western Blot Virus isolation
Rapid tests- Latex agglutination
- Dot blot assay
Immuno-fluorescence
Detection of viral nucleic acid - In situ hybridization
- PCR
Simple tests- Particle agglutination
Detection of p24 antigen
-Non-specific tests for HIV
• Blood counts– Leucopenia– Lymphocyte count less
than 400/cmm– Thrombocytopenia
• T-cell subset assay– CD4 count below
200/cmm– Normal CD4:CD8 ratio
2:1. Reversed in AIDS to 0.5:1.
• Hypergammaglobulinaemia
• Diminished CMI – Candidial, tuberculin tests.
• Lab diagnosis of opportunistic infections
• Malignancies