HIV:
1. Classification and genome
a. Family: retroviruses; namely lentivirus subgroup
b. Genome: diploid; 2 single stranded, positive polarity RNA.
c. Most complex retrovirus
2. Structure
a. Bar shaped (type D) core, surrounded by lipoprotein envelope
b. 3 essential viral enzymes within nucleocapsid
i. Reverse transcriptase
ii. Integrase
iii. Protease
3. Genes and viral proteins
a. 3 standard structural genes, 6 regulatory/accessory genes
i. Gag encodes internal core proteins. most important
p24 protein (non varying antigen)
ii. Pol encodes the 3 enzymes; RTase, integrase, protease
iii. Env encodes precursor glycoprotein, gp160
iv. Gp160 cleaved into gp120 and gp41
v. Gp120 protrudes from surface, organ of attachment
vi. Gp41 mediates fusion of envelope with host cell
membrane.
vii. Mutation of env antigenic diversity
b. Regulatory/accessory genes
i. Tat and rev genes need for viral replication
ii. Tat enhances transcription
iii. 4 accessory genes
1. Nef
2. Vif
3. Vpr
4. Vpu
iv. Nef protein represses synthesis of class I MHC proteins
reduced ability of cytotoxic T cells
v. Vif protein enhances infectivity counteracts
APOBEC3G, a host enzyme that induces
hypermutations in viral DNA.
4. Host cells, receptors, pathogenesis
a. Target cells:
i. Only humans are affected by HIV
ii. Infects and kills CD4-positive helper T lymphocytes
, iii.
Profound suppression of cell-mediated immunity
iv.Predisposition to opportunistic infections.
b. Viral
entry
i.
HIV requires 2 receptors
ii.
Gp120 binds to CD4 protein on cell surface, then interacts
with second chemokine co-receptor, CCR5 or CXCR4
c. Integration
i. RTase synthesizes DNA copy of genome
ii. The copy migrates to the nucleus integrates into host
DNA by integrase establish lifelong infection
5. Immune evasion
a. 3 mechanisms
i. Integrating its DNA into the host cell genome to establish
permanent latent infection
ii. Maintain high mutation rate in env to generate variable
antigens
iii. Tat and Nef proteins production which downregulates
class I MHC proteins
Transmission
3 routes:
Sexual contact:
Predominant mode of transmission
Risk of acquiring virus is higher in uncircumcised males, and other STD
patients
Transfer of infected blood:
Occur through IV drug use with shared needles, needle-stick injuries or
blood transfusions
Perinatal (vertical) transmission:
Infected mother can transmit the virus to infant via placenta or breast
milk.
Over 50% neonatal infections happen at the time of delivery
Pathogenesis:
1. Cellular entry and replication
a. Virus initially infects dendritic cells in mucosa, then CD4-positive
helper T lymphocytes.
b. Viral envelope glycoprotein gp120 binds to CD4 receptor on cell
surface and a second chemokine co-receptor (CCR5
macrophage-tropic or CXCR4 T-cell tropic strain)
1. Classification and genome
a. Family: retroviruses; namely lentivirus subgroup
b. Genome: diploid; 2 single stranded, positive polarity RNA.
c. Most complex retrovirus
2. Structure
a. Bar shaped (type D) core, surrounded by lipoprotein envelope
b. 3 essential viral enzymes within nucleocapsid
i. Reverse transcriptase
ii. Integrase
iii. Protease
3. Genes and viral proteins
a. 3 standard structural genes, 6 regulatory/accessory genes
i. Gag encodes internal core proteins. most important
p24 protein (non varying antigen)
ii. Pol encodes the 3 enzymes; RTase, integrase, protease
iii. Env encodes precursor glycoprotein, gp160
iv. Gp160 cleaved into gp120 and gp41
v. Gp120 protrudes from surface, organ of attachment
vi. Gp41 mediates fusion of envelope with host cell
membrane.
vii. Mutation of env antigenic diversity
b. Regulatory/accessory genes
i. Tat and rev genes need for viral replication
ii. Tat enhances transcription
iii. 4 accessory genes
1. Nef
2. Vif
3. Vpr
4. Vpu
iv. Nef protein represses synthesis of class I MHC proteins
reduced ability of cytotoxic T cells
v. Vif protein enhances infectivity counteracts
APOBEC3G, a host enzyme that induces
hypermutations in viral DNA.
4. Host cells, receptors, pathogenesis
a. Target cells:
i. Only humans are affected by HIV
ii. Infects and kills CD4-positive helper T lymphocytes
, iii.
Profound suppression of cell-mediated immunity
iv.Predisposition to opportunistic infections.
b. Viral
entry
i.
HIV requires 2 receptors
ii.
Gp120 binds to CD4 protein on cell surface, then interacts
with second chemokine co-receptor, CCR5 or CXCR4
c. Integration
i. RTase synthesizes DNA copy of genome
ii. The copy migrates to the nucleus integrates into host
DNA by integrase establish lifelong infection
5. Immune evasion
a. 3 mechanisms
i. Integrating its DNA into the host cell genome to establish
permanent latent infection
ii. Maintain high mutation rate in env to generate variable
antigens
iii. Tat and Nef proteins production which downregulates
class I MHC proteins
Transmission
3 routes:
Sexual contact:
Predominant mode of transmission
Risk of acquiring virus is higher in uncircumcised males, and other STD
patients
Transfer of infected blood:
Occur through IV drug use with shared needles, needle-stick injuries or
blood transfusions
Perinatal (vertical) transmission:
Infected mother can transmit the virus to infant via placenta or breast
milk.
Over 50% neonatal infections happen at the time of delivery
Pathogenesis:
1. Cellular entry and replication
a. Virus initially infects dendritic cells in mucosa, then CD4-positive
helper T lymphocytes.
b. Viral envelope glycoprotein gp120 binds to CD4 receptor on cell
surface and a second chemokine co-receptor (CCR5
macrophage-tropic or CXCR4 T-cell tropic strain)
