Virology

1. HIV Disease and AIDS
Historical Background
1981 : Few reports about a rare disease in previously
healthy homosexual men with high incidence of :
•Loss of immune function
•Unusual opportunistic infections
•Certain malignant tumors
1982 : Word AIDS was used 1st
time by CDC
1983 : Viral cause was identified that selectively infects Th cells
Was named as HTLV-III
Now named as HIV (Human Immunodeficiency Virus)

2. Epidemiology
• Worldwide >33 millions infected with HIV
• Number 1 killer in Africa
• >20 millions have died of AIDS
• 4th
leading cause of death in the world after
heart diseases, strokes & pneumonia
• A new infection occurs every 6 seconds
• A person dies of AIDS every 5 minutes
HIV Disease and AIDS

5. Routes of Transmission &
Persons at High Risk
1. Sexual contact
o Homosexual men : major infected group
2. Blood & Blood Products
o Drug abusers &
o Hemophiliacs
3. Mother to infant
o During child birth
o Breast feeding
HIV Disease and AIDS

6. Causative Agent
• HIV-1 : in most parts of the world
• HIV-2 : in most parts of Africa & India
• Family : Retroviridae
• Subgroup : Lentivirus
HIV Disease and AIDS

7. Structure of virus
Important antigens
• Surface glycoprotein (gp120)
o Partly responsible for attachment
to host cells
• Transmembrane glycoprotein
(gp41)
o Probably plays a role in entry of
virus into cell
• Matrix protein (p17)
o Helps maintain viral structure
HIV Disease and AIDS

8. Structure of virus
The Core of Virion
• Capsid antigen (p24)
• Two copies of ssRNA
• Nucleocapsid
• Viral enzymes
o Reverse transcriptase
o Protease
o Integrase
HIV Disease and AIDS

10. Types of Human Cells affected
• CD4+
Th1 cells :
o Principal target of HIV
o Main cause of immunodeficiency
• CD4+
Th2 cells
• CD4+
macrophages, dendritic & other APC
o Are continuing source of virus
• Several types of brain cells
o Probable cause of lethargy & dementia
• Intestinal epithelium & lymphoid tissues
o Probably contribute to chronic diarrhea & weight loss

12. Attachment, Entry & Replication of virus inside host cell

13. HIGH GENETIC VARIABILITY IN HIV
• Is due to high rate of error when reverse
transcriptase copies viral genome
• Variant viruses show differences in:
o Their preferred host cell
o Rate of replication
o Response to host immunity
• Enormously complicates the development
of vaccine against HIV

14. CLINICAL COURSE OF HIV DISEASE

16. CLINICAL FEATURES OF HIV DISEASE
A. Acute Retroviral
syndrome (ARS)
• Incubation period 1-6 weeks
• In 50-70% of HIV infected
subjects
• Sore throat & Fever
• Myalgia & headache
• Enlarged lymph nodes
• Symptoms may last for 1-4
weeks
• Self-limiting without treatment

17. B. Asymptomatic period
• Lasts for months to years
• A silent struggle goes on between HIV &
immune system
• The virus continues to be present in blood and
body secretions – a threat to others
• Level of CD+ lymphocytes slowly falls
• Leads to AIDS
CLINICAL FEATURES OF HIV DISEASE

18. C. AIDS
• The immune system slowly loses battle
• Peripheral blood CD+ count slowly falls
• Symptoms of AIDS appear when count falls
below 300 cells per ul (Normal count 1000 cells per ul)
Incubation period
• 10% - 5 years ; 90% within 17 years
• Weight loss, fatigue, diarrhea, fever
• Enlarged lymph nodes
• Opportunistic infections
• Malignant tumors
CLINICAL FEATURES OF HIV DISEASE

19. Malignant Tumours Associated with AIDS
• Kaposi’Sarcoma
o Unusual tumor arising from blood or lymphatic vessels
o Caused by herpes virus-8
o Strong association with immunodeficiency
• B-Lymphocytic Tumors of Brain
o 60-100 times more common in AIDS
• Cervical & Anal Carcinomas

21. • Pneumocystosis :
o Pneumocystis carinii
• Toxoplasmosis :
o Toxoplasma gondii
• Cytomegalovirus Disease : CMV
• Tuberculosis
o M. tuberculosis &
o M. avium-intracellulare complex
• Candidiasis
Opportunistic infections
Associated with AIDS

23. Lab Diagnosis
• anti-HIV Abs by ELISA: Easier to
detect than virus itself
• Confirmed by Western Blot & RIBA
• PCR : to detect viral RNA

24. Mechanism of action of antiretroviral drugs
NRTI
(Nucleoside
RT Inhibitors)
•Ziduvudine
•Stavudine NNRTI
(Nonnucleoside
RT Inhibitors)
•Nevirapine
•Delaviridine
TREATMENT OF AIDS
• A cocktail of drugs with different mechanisms of action
• HAART “Highly Active Antiretroviral Therapy”
• Specific treatment for opportunistic infections

25. • Health education
• Detection & Treatment of the HIV-pos cases
• Changing sexual behaviors
• Disinfection of all blood samples
• Chemoprophylaxis with Ziduvidine to
o HIV-positive pregnant mother &
o Newborn infants to HIV-positive mother
• Treatment of opportunistic infections
PREVENTION OF AIDS

26. HIV Vaccine Prospects
• No approved vaccine is currently available
• A vaccine that is a combination of two previously
unsuccessful vaccine candidates was reported in
September 2009 to have resulted in a 30% reduction
in infections in a trial conducted in Thailand
• Theoretically two approaches:
1. Preventive Vaccine
o To immunize uninfected persons
2. Therapeutic vaccine
o To boost the immunity of already infected persons
o Like post-exposure treatment of rabies
PREVENTION OF AIDS