1. Human Immunodeficiency Virus and Acquired Immunodeficiency Syndromes
Dongli Pan
Department of Medical Microbiology and Parasitology
Zhejiang University School of Medicine

2. Baltimore classification
DNA viruses
RNA viruses
Baltimore classification
Fields Virology, 6th edition

3. People estimated to be living with HIV (2014)

4. How was HIV discovered
In , 5 young men, all active homosexuals, were treated for Pneumocystis carinii pneumonia (PCP) in LA, CA. The symptoms suggest the possibility of cellular-immune dysfunction.
Clusters of PCP and Kaposi’s sarcoma observed in other hospitals.
1982 disease started to be called AIDS.
Found transmitted at birth and heterosexually.
Virus was first isolated in 1983 from the lymph node of a patient with lymphadenopathy in Paris.
1984 Electron microscopy and sequence analysis revealed HIV to be a lentivirus, known group of retroviruses.

5. Where is HIV from

6. Structure of HIV particle
• Core
– +ssRNA 2copies
– reverse transcriptase
(RT, an RNA dependent DNA polymerase)
– P24
• Envelope
--gp120
--gp41
(P24)
Diameter: ~ 100 nm

7. HIV genome 1 RNA (~ 10 kb), 9 genes
long terminal repeat, LTR (5’, 3’- end)
3 structural genes
– gag → P55 → P24, P17, P6, P7
– pol → RT, integrase, RNase H and protease
– env → glycoprotein (gp120 and gp41)
6 regulator genes
tat, rev and nef are most important
长末段重复序列

8. Replication cycle of HIV
Watch video:

9. HIV entry: one receptor, two co-receptors
Receptor: CD4
Coreceptor: CCR5/CXCR4
HIV targets CD4+ cells. The major targets are CD4+ T cells. But it can also infect monocytes, macrophages, dendritic cells, etc.

10. HIV types and subtypes HIV’s genome is highly variable
Reverse transcriptase of HIV does not have proofreading activity
HIV has two types: HIV-1 and HIV-2
HIV-1 is more common, more virulent and more infectious than HIV-2
Each type has many subtypes

11. Transmission of HIV
Source: HIV carriers and AIDS patients
HIV is transmitted by certain body fluids such as blood, semen, vaginal fluids and breast milk.
HIV is usually not transmitted by saliva.

12. China’s National Health and Family Planning Commission

13. Pathogenesis of HIV Damage monocytes and macrophages at early stages.
Damage CD4+ T cells. As infection progresses HIV mainly infects CD4+ T cells and causes depletion of CD4+ T cells by
1) HIV-induced cell lysis,
2) killing of infected cells by cytotoxic T cells and
3) Inhibition of their production.
Damage other immune cells: B cells and NK cells.
The damaged immune system (especially with very low CD4 T cell levels) cannot control opportunistic infections and cancer, resulting in AIDS.

14. Three stages of HIV infection

15. Three stages of HIV infection
Acute infection: fever, rash, night sweats, muscle aches, sore throat, fatigue, swollen lymph nodes, etc. 2-4 weeks.
Clinical latency: no symptoms; serum positive for HIV antibodies years (8 years in average)
AIDS period:
Systematic symptoms: prolonged fever, night sweats, fatigue, swollen lymph nodes, diarrhea.
Infection of the CNS: Memory loss, depression, and other neurological disorders
Cancer
Opportunistic infections

16. Opportunistic infections
Bacterial infections
mycobacterium avium complex
鸟型分支杆菌
Mycobacterium tuberculosis
结核分支杆菌
Viral infections
Herpes simplex virus
Cytomeglovirus
Varicella-zoster virus
Kaposi’s sarcoma herpes virus
Fungal infection
Candida 念珠菌
Coccidioides 球孢子菌
Histoplasma 组织包浆菌
Pneumocystis 肺囊虫
Cryptococcus 隐球菌（致脑膜炎）
Protozoan parasites
Cryptosporidium 隐孢子虫
Toxoplasma 弓形虫
Cancer
Kaposi’s sarcoma
Lymphoma
Cervical cancer

17. Diagnosis of HIV 1. Serology tests: 2. qRT-PCR Screening tests:
ELISA. Can distinguish HIV-1 and HIV-2. Can have false positives.
b) Confirmation tests:
Western blot
c) Rapid antibody tests:
Takes 20 min. Less acurate
2. qRT-PCR

18. HIV treatment
Inhibitors of HIV replication block various steps

19. Zidovudine （Azido-deoxythymidine)
齐多夫定
A nucleoside analog that inhibits RT.

20. Highly active antiretroviral therapy=HAART
Combination therapy
Highly active antiretroviral therapy=HAART
HAART is a combination of at least 3 antiviral drugs, usually 1 protease inhibitor and 2 RT inhibitors.
Efficient>80% of those who receive a therapy. Reduction of viral replication < 100 copies/mL
But,
There is as yet no cure!
AIDS therapy is expensive.
Drug resistant viruses appear.
Can’t stop taking the drugs.
There is no vaccine.
Why so difficult to treat?
Fast mutation rate: drug resistance
Infecting the immune system: the immune system cannot help eliminate the virus.
Integration into the host genome: latent reservoir persists

21. Azido-deoxythymidine (AZT)
A nucleoside analog that inhibits RT.

22. Non-nucleoside RT inhibitors (NNRTI)

23. Highly active antiretroviral therapy=HAART
Combination therapy
Highly active antiretroviral therapy=HAART
HAART is a combination of at least 3 antiviral drugs, usually 1 protease inhibitor and 2 RT inhibitors.
Efficient>80% of those who receive a therapy. Reduction of viral replication < 100 copies/mL
Reduction in the number of AIDS-affected persons and AIDS-deaths in USA and Western Europe
But,
There is as yet no cure!
AIDS therapy is expensive.
Can’t stop taking the drugs.
There is no vaccine.