1. Retroviruses 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. Retroviridae HIV Human Immunodeficiency Virus
AIDS Acquired ImmunoDeficiency Syndromes

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

5. History
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 was 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.

7. 1. Biological properties
1) Structure
• Nucleocapsid
– +ssRNA 2copies
– reverse transcriptase
(RT, an RNA dependent DNA polymerase)
– P24
• Envelope
– P17
– lipid bilayer membrame
--gp120
--gp41
(P24)
Diameter: ~ 100 nm

8. HIV under electron microscope

9. 2) Genome 2 copies of 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

10. Entry of HIV: receptor and coreceptor
Receptor: CD4
Coreceptor: CCR5/CXCR4
Infect CD4+ T cells, monocytes, macrophages, dendritic cells, microglial cells

11. Replication Watch video:
provirus
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12. 4) Genetic variability
HIV reverse transcriptase has no proof-reading function.
Hard to develop antiviral drugs and vaccines against HIV.
Multiple subtypes:
Type 1: HIV-1 (more common and pathogenic)
Subtypes: A, B, C, D, F, G, H, J, K and CRFs (circulating recombinant forms)
Type 2: HIV-2
Subtypes: A to H, only A and B epidemic

13. HIV types and subtypes HIV types: HIV-1 and HIV-2 HIV-1 subtypes:

14. 2. Transmission
Source: HIV carriers and AIDS patients
HIV is transmitted by certain body fluids such as blood, semen, vaginal fluids and breast milk.
HIV is NOT transmitted by saliva.

15. China’s National Health and Family Planning Commission

16. 3. Clinical manifestation: 3 stages
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:
Systematic symptoms: prolonged fever, night sweats, fatigue, swollen lymph nodes, diarrhea.
Infection of the CNS: Memory loss, depression, and other neurological disorders
Cancer (as a result of immune system dysregulation and replication of oncogenic viruses)
Opportunistic infections

17. Opportunistic infections
Bacterial infections
mycobacterium avium complex
Mycobacterium tuberculosis
Viral infections
Herpes simplex virus
Cytomeglovirus
Varicella-zoster virus
Koposi’s sarcoma herpes virus
Fungal infection
Candida
Coccidioides
Histoplasma
pneumocystis
Cryptococcus
Protozoan parasites
Cryptosporidium
Toxoplasma
Cancer
Koposi’s sarcoma
Lymphoma
Cervical cancer

18. 4. Pathogenesis 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.
Lower activity of 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.

20. Immune response to HIV infection
Cellular immune response: CTL and NK cells
Humoral immune response: HIV antibodies
However immunity cannot eliminate HIV
Lymphocytes and macrophages are damaged
CD4 helper T cells are damaged
Antigenic drift of gp120 protein
Latent infection

21. 5. Diagnosis 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

22. 6. Treatment Difficulties in treating HIV
Fast mutation rate: drug resistant virus constantly emerge.
Infecting the immune system: the immune system cannot help eliminate the virus.
Integration into the host genome: once integrated, it is hard to remove.

23. Inhibitors of HIV replication block various steps

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

25. Non-nucleoside RT inhibitors (NNRTI)

26. 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.

27. Hope

28. Retroviridae
HTLV Human T-Lymphotropic Virus-1

29. Human T-lymphotropic virus -1 (HTLV-1)
Biological features and transmission are similar to HIV
Associated diseases
Malignances
Adult T cell leukemia
Inflammatory diseases
Spastic paraparesis
Arthropathy