HIV Replication and Pathogenesis

Question 1

What type of disease is HIV?

Answer 1

Zoonotic disease

Question 2

What are the modern routes of HIV transmission?

Answer 2

• Unprotected sex
• Sharing needles with infected persons
• Transmission from infected mother to fetus (rare)
• Infection from blood products (rare)

Question 3

Who are more likely to get infected with HIV? Men or women?

Answer 3

Women

Question 4

By what routes does HIV disseminate?

Answer 4

Lymphoid cells embedded in vag and rectum epithelium and spreads to lymph nodes

Question 5

Typical Syx of acute HIV infection

Answer 5

• Fever
• Weight loss
• Mouth sores
• Malaise

Question 6

Describe viral characteristics of HIV

Answer 6

• RNA virus
• Lentivirus (slow to cause diease)
• ssRNA (+) strand
• Two copies of genetic info (diploid)

Question 7

What two receptors are needed for HIV to bind to CD4 helper cells?

Answer 7

• CD4 receptor
• Chemokine receptor

Question 8

What chemokine receptor is a target in early HIV? Late?

Answer 8

• Early - Beta-chemokine receptor (CCR5) (macrophages)
• Late - Alpha-chemokine receptor (CXCR4) (TCells)

Question 9

What mutations in HIV allow it to form T cell syncitia?

Answer 9

Mutains in Env allow the virus to bind CXCR4 instead of CCR5 and form syncitia!

Question 10

Describe the process of HIV attachment

Answer 10

• HIV Env is composed of TM (transmembrane [gp41]) and SU (surface [gp120])
• The SU binds to the CD4 and then to one of the chemokine receptors (depending on cell)
• TM extends and sticks fusion peptide in cell membrane

Question 11

What is the general process of HIV uncoating?

Answer 11

• Attachment and membrane fusion
• Uncoating and partial capsid disintegration
• Reverse transcription of ssRNA genomes to DNA
• Migration of circular genomes to nucleus

Question 12

What are the key points of reverse transcription?

Answer 12

• tRNA bound to ssRNA is a primer
• Templates witch during replication

Question 13

Where does the HIV provirus integrate?

Answer 13

• At site of active genes

Question 14

For how long does the viral genome become part of the cell?

Answer 14

For the life of the cell. This event is permanent

Question 15

What is the primary obstacle to eradicating HIV?

Answer 15

Latency

Question 16

What marks the end of phase 1 of HIV replication?

Answer 16

Integration

Question 17

What marks the start of phase 2 of HIV replication?

Answer 17

Recruitment of RNA Pol II and the transcription, splicing, and exportation of the mRNA to the cytoplasm

Question 18

Where does translation of HIV proteins occur?

Answer 18

Cytoplasm

Question 19

From where is the HIV genome derived?

Answer 19

Full-length mRNA transcripts

Question 20

What do short mRNAs encode for?

Answer 20

Env

Question 21

Where is Env mRNA translated?

Answer 21

At the rough ER

Question 22

Where is Env processed?

Answer 22

In the Golgi it is glycosylated, cleaved

Question 23

Where do proteins and genomic mRNAs accumulate before the virion buds?

Answer 23

At the plasma membrane in lipid rafts

Question 24

What is the infectious dose of the virion following budding from the cell?

Answer 24

Virions are not infectious

Question 25

What process makes HIV virions infectious?

Answer 25

**Protease** cleavage of Gag into subunits within the virion

Question 26

What process do anti-protease drugs try to inhibit?

Answer 26

Inhbition of the Gag polyprotein into its three subunits MA, CA, and NC. When these three domains are cleaved into subunits, the particle becomes infectious

Question 27

What makes Env such a vital contributor to HIV's virulence?

Answer 27

It leads to the formation of syncytia which can cause immunodeficiency

Question 28

Describe the pathogenesis that leads to massive Tcell loss

Answer 28

1. Freshly infected T cells are activated and secrete abnormal cytokines 2. Cytokines may kill bystander T cells 3. HIV accumulates mutations and escapes immune control 4. CXCR4 tropic viruses emerge and T cell losses accelerate 5. Opportunistic infections and cancer cannot be fought resulting in patient death

Question 29

HIV was first transmitted to humans by what animal?

Answer 29

Chimpanzees

Question 30

Following entry, what are the next steps of HIV lifecycle?

Answer 30

* Conversion to DNA * Cicularization * Migration to the nucleus * Integration into the chromosome

Question 31

What enzyme is used to synthesize the genomic mRNAs that are packaged intot eh HIV virion?

Answer 31

RNA polymerase II

Question 32

What do high rates of virion production and T cell turnover create?

Answer 32

A dynamic equilibrium that allows virus mutants to emerge