Human Immunodeficiency Virus

Question 1

Stages

Answer 1

Attachment
Penetration and Uncoating
Reverse Transcription and Integration
Immediate Early Gene Expression
Early Gene Expression
Late Gene Expression
Assembly and Release
Maturation

Question 2

Attachment

Answer 2

• virion spike gp120 (SU) attaches to CD4 receptor on host cell

Question 3

Penetration and Uncoating

Answer 3

• gp120 binds to coreceptor (CXCR4, CCR5) which triggers a conformational change in the spike
• gp41 (TM) extends to impale the host plasma membrane
• virion envelope and plasma membrane fuse
• nucleocapsid core enters host cell cytoplasm

Question 4

Reverse Transcription and Integration

Answer 4

• occurs in nucleocapsid core in cytoplasm of infected host cell
• reverse transcription converts (+)ssRNA to greater than full length linear dsDNA with long terminal repeats forming preintegration complex (with NLS)
• preintegration complex into into host chromosome using integrase and gaps are repaired by cellular enzymes

Question 5

Immediate Early Gene Expression

Answer 5

• initial transcription of proviral DNA depends only on host cell transcription factors and DdRp II that binds to LTR sequences
• primary transcript is capped, polyadenylated, and most are spliced before export to cytoplasm
• translation of spliced mRNA produces Tat regulatory protein

Question 6

Early Gene Expression

Answer 6

• Tat protein revs up LTR transcription
• primary transcript capped, polyadenylated, and most are spliced before export to cytoplasm
• translation of the spliced mRNA produces accessory proteins ENV, Tat, and Rev

Question 7

Late Gene Expression

Answer 7

• Tat protein still activating LTR transcription
• Rev protein has NLS and NES and undergoes cytoplasmic shuffling
• Rev binds to RRE and promotes nuclear export of unspliced viral mRNA
• NES on Rev causes rapid nuclear export of bound viral RNA
• Unspliced, viral genomic RNA translated on free, cytoplasmic ribosomes to produce GAG and GAG-POL (-1 frameshift)
  
  • no co-translational cleavage occurs
  • migrate to plasma membrane for assembly and budding
• spliced ENV mRNA translated on RER
  
  • co-translationally extruded into ER lumen
  • glycosylation occurs on SU and TM subunits
  • cleavage by furin in trans-Golgi to separate gp120(SU) and gp41 (TM) subunits
  • spikes are trafficked to plasmam membrane for assembly and budding

Question 8

Assembly and Release

Answer 8

• GAG and GAG-POL proteins associate with viral RNA at plasma membrane where spikes has accumulated
• polyprotein cleavage drive budding

Question 9

Maturation

Answer 9

• occurs only after release

- cleavage by viral protease to give nucleocapsid its distinctive cone shape