HIV Replication and Pathogenesis Flashcards

1
Q

What type of disease is HIV?

A

Zoonotic disease

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2
Q

What are the modern routes of HIV transmission?

A
  • Unprotected sex
  • Sharing needles with infected persons
  • Transmission from infected mother to fetus (rare)
  • Infection from blood products (rare)
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3
Q

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

A

Women

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4
Q

By what routes does HIV disseminate?

A

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

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5
Q

Typical Syx of acute HIV infection

A
  • Fever
  • Weight loss
  • Mouth sores
  • Malaise
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6
Q

Describe viral characteristics of HIV

A
  • RNA virus
  • Lentivirus (slow to cause diease)
  • ssRNA (+) strand
  • Two copies of genetic info (diploid)
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7
Q

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

A
  • CD4 receptor
  • Chemokine receptor
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8
Q

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

A
  • Early - Beta-chemokine receptor (CCR5) (macrophages)
  • Late - Alpha-chemokine receptor (CXCR4) (TCells)
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9
Q

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

A

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

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10
Q

Describe the process of HIV attachment

A
  • 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
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11
Q

What is the general process of HIV uncoating?

A
  • Attachment and membrane fusion
  • Uncoating and partial capsid disintegration
  • Reverse transcription of ssRNA genomes to DNA
  • Migration of circular genomes to nucleus
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12
Q

What are the key points of reverse transcription?

A
  • tRNA bound to ssRNA is a primer
  • Templates witch during replication
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13
Q

Where does the HIV provirus integrate?

A
  • At site of active genes
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14
Q

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

A

For the life of the cell. This event is permanent

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15
Q

What is the primary obstacle to eradicating HIV?

A

Latency

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16
Q

What marks the end of phase 1 of HIV replication?

A

Integration

17
Q

What marks the start of phase 2 of HIV replication?

A

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

18
Q

Where does translation of HIV proteins occur?

A

Cytoplasm

19
Q

From where is the HIV genome derived?

A

Full-length mRNA transcripts

20
Q

What do short mRNAs encode for?

A

Env

21
Q

Where is Env mRNA translated?

A

At the rough ER

22
Q

Where is Env processed?

A

In the Golgi it is glycosylated, cleaved

23
Q

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

A

At the plasma membrane in lipid rafts

24
Q

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

A

Virions are not infectious

25
Q

What process makes HIV virions infectious?

A

Protease cleavage of Gag into subunits within the virion

26
Q

What process do anti-protease drugs try to inhibit?

A

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

27
Q

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

A

It leads to the formation of syncytia which can cause immunodeficiency

28
Q

Describe the pathogenesis that leads to massive Tcell loss

A
  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
29
Q

HIV was first transmitted to humans by what animal?

A

Chimpanzees

30
Q

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

A
  • Conversion to DNA
  • Cicularization
  • Migration to the nucleus
  • Integration into the chromosome
31
Q

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

A

RNA polymerase II

32
Q

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

A

A dynamic equilibrium that allows virus mutants to emerge