Retroviruses Flashcards
What are some unique features of retroviruses?
☛ They undergo reverse transcription.
☛ All retroviruses have three common genes i.e: gag, pol and env genes.
☛ They have two copies of ss(+)sense RNA [Baltimore Group 6].
Even though retroviruses have positive-sense RNA, they undergo reverse transcription, instead of directly using their RNA as mRNA. Why is this so?
This is because retroviruses need to integrate their genetic material into the host cell’s DNA to establish a persistent infection.
[The positive-sense RNA genome is reverse-transcribed into complementary DNA (cDNA) by the enzyme reverse transcriptase. This cDNA is then integrated into the host cell’s genome by another viral enzyme called integrase.]
Briefly state the function of each of the following genes common to retroviruses:
(a) env gene
(b) gag gene
(c) pol gene
(a) env gene: encodes envelope proteins crucial for viral attachment and penetration
(b) gag gene: encodes for structural proteins like the matrix, capsid and nucleocapsid proteins
(c) pol gene: encodes enzymes necessary for viral replication e.g. reverse transcriptase, integrase and protease
HIV
(a) Family: ____________
(b) Genus: ____________
(c) Species: ____________
(a) Retroviridae
(b) Lentiviruses
(c) HIV-1 and HIV-2
Comment on the groups and clades of HIV-1.
HIV-1 is divided into 4 groups: M (Major), N, O and P.
Group M is further divided into clades (subtypes): A, B, C, D, F, G, H, J and K. These subtypes can also recombine to form Circulating Recombinant Forms (CRFs), which are hybrid viruses with genetic material from multiple subtypes.
Compare HIV-1 and HIV-2 using the following criteria:
(a) Distribution
(b) Transmission
(c) Progression
(d) Treatment
(e) Origin
(a) Distribution
HIV-1: worldwide
HIV-2: West Africa, Europe, USA
(b) Transmission
HIV-1: Easier transmission
HIV-2: Less easily transmitted
(c) Progression
HIV-1: faster progression
HIV-2: slower progression
(d) Treatment
HIV-1: responds to NNRTIs
HIV-2: no response to NNRTIs
(e) Origin
HIV-1: related to SIVcpz (Chimpanzee SIV)
HIV-2: related to SIVsm (Sooty Mangabey SIV)
Further notes:
NNRTIs stand for Non-Nucleoside Reverse Transcriptase Inhibitors. These are a class of antiretroviral drugs used to treat HIV by inhibiting the reverse transcriptase enzyme, which is crucial for the virus to replicate.
Discuss the structure of the HIV virus. [envelope, matrix, capsid, RNA genome, enzymes, accessory proteins]
(a) Envelope: This is the outermost layer comprised of a lipid bilayer derived from the host cell membrane. Embedded in this envelope are viral glycoproteins such as gp120 and gp41, which are crucial for the virus to attach and fuse with host cells.
(b) Matrix: Just beneath the viral envelope is the matrix, made up of the protein p17. This layer provides structural support and helps in the assembly of new virions.
(c) Capsid: The core of the virus is enclosed in a cone-shaped capsid made of the protein p24. This capsid protects the viral RNA and associated enzymes.
(d) RNA Genome: HIV virus contains two copies of single-stranded RNA.
(e) Enzymes: Within the capsid, there are several key enzymes:
Reverse transcriptase - converts viral RNA into DNA
Integrase - integrates the viral DNA into the host cell’s genome.
Protease - cleaves newly synthesized polyproteins to create mature viral proteins
(f) Accessory proteins: HIV also has several accessory proteins, such as Nef, Vif, Vpr and Vpu, which help the virus evade the host immune system and enhance its replication.
[Diagram 1] [Diagram 2]
[Image 1] [Image 2] [Image 3] [Image 4]
Discuss HIV ligand - cell receptor interaction.
✪ The HIV envelope glycoprotein gp120 binds to the CD4 receptor.
✪ After binding to CD4, gp120 undergoes a conformational change that allows it to interact with a co-receptor, either CCR5 or CXCR4.
✪ The binding of gp120 to the co-receptor triggers another conformational change in the HIV envelope glycoprotein gp41, facilitating the fusion of the viral envelope with the host cell membrane.
Further notes:
The CD4 receptor is primarily found on the surface of T-helper cells, macrophages and dendritic cells.
CCR5 is a chemokine receptor found on the surface of various immune cells, including T cells, macrophages, and dendritic cells. It is involved in the immune response by binding to chemokines, which are signaling molecules that direct the movement of immune cells to sites of inflammation or infection.
CXCR4 is another chemokine receptor that is widely expressed on various cell types, including immune cells, endothelial cells, and neurons. It is involved in the regulation of cell migration, particularly in the immune system and during embryonic development.
Summarize the retrovirus replication cycle beginning from reverse transcription and ending at budding and maturation.
➤ Viral RNA is reverse-transcribed into DNA by the enzyme reverse transcriptase.
➤ The newly synthesized viral DNA is transported into the nucleus and integrated into the host cell genome by the enzyme integrase.
➤ The integrated viral DNA is transcribed into RNA, which is then translated into viral proteins by the host cell’s machinery.
➤ New viral RNA and proteins are assembled into immature viral particles at the host cell membrane.
➤ The immature viral particles bud off from the host cell, acquiring a portion of the host cell membrane as their envelope.
➤ The viral protease enzyme processes the viral proteins, resulting in mature, infectious viral particles.
➤ [Diagram 1] [Diagram 2]
List the modes of transmission of HIV.
sexual contact [vaginal, anal, oral], contaminated needles/blades, blood transfusion, mother-to-child transmission [during pregnancy, delivery or breastfeeding]
What are some of the risk factors in the acquisition of HIV infection?
📝 dose of HIV inoculum
📝 host susceptibility to infection
📝 routes of transmission [intravenous > rectal > vaginal]
📝 mucosal inflammation [ulceration by STDs]
List the stages in the progression of HIV infection and give a brief description of each.
(1) Primary stage/acute retroviral syndrome
Flu-like symptoms such as fever, headache, rash, and swollen lymph nodes. Some people may not experience noticeable symptoms.
(2) Asymptomatic stage
Often asymptomatic, but some indivuduals may experience mild symptoms. HIV continues to replicate at low levels. The immune system gradually weakens over time.
(3) Symptomatic stage and full blown AIDS
The immune system is severely damaged; CD4 count drops below 200 cells/mm³. Opportunistic infections and cancers begin to emerge. Symptoms include rapid weight loss, recurring fever, extreme fatigue, and prolonged swelling of lymph nodes.
What are some common protozoal opportunistic infections associated with AIDS?
PCP pneumonia, toxoplasmosis, crytosporidiosis,
Isosporiasis
What are some common fungal opportunistic infections associated with AIDS?
Candidiasis, Cryptococcosis, Histoplasmosis, Coccidioidomycosis
Further notes:
Candidiasis
Cause: Candidiasis is caused by an overgrowth of Candida species, particularly Candida albicans.
Symptoms: It can affect various parts of the body, leading to oral thrush (white patches in the mouth), vaginal yeast infections (itching, discharge), and invasive candidiasis (affecting the bloodstream and internal organs).
Cryptococcosis
Cause: Cryptococcosis is caused by Cryptococcus neoformans or Cryptococcus gattii, which are found in soil and bird droppings.
Symptoms: It primarily affects the lungs and central nervous system, causing pneumonia-like symptoms or meningitis (fever, headache, neck stiffness).
Histoplasmosis and Coccidioidomycosis (Valley Fever) cause flu/pneumonia-like symptoms.
What are some common bacterial opportunistic infections associated with AIDS?
TB, MAC [Mycobacterium avium complex], Salmonella septicaemia
