HIV Replication and Pathogenesis Flashcards
What type of disease is HIV?
Zoonotic disease
What are the modern routes of HIV transmission?
- Unprotected sex
- Sharing needles with infected persons
- Transmission from infected mother to fetus (rare)
- Infection from blood products (rare)
Who are more likely to get infected with HIV? Men or women?
Women
By what routes does HIV disseminate?
Lymphoid cells embedded in vag and rectum epithelium and spreads to lymph nodes
Typical Syx of acute HIV infection
- Fever
- Weight loss
- Mouth sores
- Malaise
Describe viral characteristics of HIV
- RNA virus
- Lentivirus (slow to cause diease)
- ssRNA (+) strand
- Two copies of genetic info (diploid)
What two receptors are needed for HIV to bind to CD4 helper cells?
- CD4 receptor
- Chemokine receptor
What chemokine receptor is a target in early HIV? Late?
- Early - Beta-chemokine receptor (CCR5) (macrophages)
- Late - Alpha-chemokine receptor (CXCR4) (TCells)
What mutations in HIV allow it to form T cell syncitia?
Mutains in Env allow the virus to bind CXCR4 instead of CCR5 and form syncitia!
Describe the process of HIV attachment
- 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
What is the general process of HIV uncoating?
- Attachment and membrane fusion
- Uncoating and partial capsid disintegration
- Reverse transcription of ssRNA genomes to DNA
- Migration of circular genomes to nucleus
What are the key points of reverse transcription?
- tRNA bound to ssRNA is a primer
- Templates witch during replication
Where does the HIV provirus integrate?
- At site of active genes
For how long does the viral genome become part of the cell?
For the life of the cell. This event is permanent
What is the primary obstacle to eradicating HIV?
Latency
What marks the end of phase 1 of HIV replication?
Integration
What marks the start of phase 2 of HIV replication?
Recruitment of RNA Pol II and the transcription, splicing, and exportation of the mRNA to the cytoplasm
Where does translation of HIV proteins occur?
Cytoplasm
From where is the HIV genome derived?
Full-length mRNA transcripts
What do short mRNAs encode for?
Env
Where is Env mRNA translated?
At the rough ER
Where is Env processed?
In the Golgi it is glycosylated, cleaved
Where do proteins and genomic mRNAs accumulate before the virion buds?
At the plasma membrane in lipid rafts
What is the infectious dose of the virion following budding from the cell?
Virions are not infectious
What process makes HIV virions infectious?
Protease cleavage of Gag into subunits within the virion
What process do anti-protease drugs try to inhibit?
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
What makes Env such a vital contributor to HIV’s virulence?
It leads to the formation of syncytia which can cause immunodeficiency
Describe the pathogenesis that leads to massive Tcell loss
- Freshly infected T cells are activated and secrete abnormal cytokines
- Cytokines may kill bystander T cells
- HIV accumulates mutations and escapes immune control
- CXCR4 tropic viruses emerge and T cell losses accelerate
- Opportunistic infections and cancer cannot be fought resulting in patient death
HIV was first transmitted to humans by what animal?
Chimpanzees
Following entry, what are the next steps of HIV lifecycle?
- Conversion to DNA
- Cicularization
- Migration to the nucleus
- Integration into the chromosome
What enzyme is used to synthesize the genomic mRNAs that are packaged intot eh HIV virion?
RNA polymerase II
What do high rates of virion production and T cell turnover create?
A dynamic equilibrium that allows virus mutants to emerge
