Viral Pathogens II Flashcards
- During the acute phase, whilst HIV RNA is increasing what is subsequently decreasing?
The T-Cells
- When would the HIV RNA peak?
• The HIV RNA peak occurs at 6 weeks after which it decreases (clinical latency) until many years later when opportunistic infections cause the RNA levels to increase.
- What happens in a typical untreated patient of HIV?
o In a typical untreated patient, ten billion virions are made and destroyed every day during the chronic phase of a disease.
o The inexorable (cant stop) depletion of CD4 T cells during infection ultimately leads to immunodeficiency (AIDS) and mortality (via opportunistic infections).
- What is a trait of the HIV virus that is evolutionary beneficial?
•This long infection period is evolutionary beneficial to the virus because it gives the virus longer for transmission.
- What is viral load and how can we determine it?
Viral load is the number of Viral RNA genomes per ml of blood
Determined by PCR
- Explain what you would see on a graph of the levels of T cells/CD4 and Viral load against time?
AT first T cells will start to decline whilst HIV RNA increases ( primary infection)
At around 6 weeks the HIV RNA will reach a peak level and then decline (Clinical Latency-lasts years) T cells may increase slightly but then decrease slowly - due to this decrease there is onset of symptoms- years later
Opportunistic infections cause the HIV RNA to increase again and T cells to majorly decline - results in DEATH
- Why is it important for the virus to invade the immune response?
•Viruses must evade immune responses because immune cells recognise and kill cells infected by virus.
- How does the virus evade the immune cells?
- To evade this type of immune response, some viruses replicate in the immune cells whose function is to recognize and kill infected cells.
- Replication in immune cells hides the virus from immune cells and inhibits immune cell function.
- Inhibition of immune cell function allows other pathogens to replicate in virus infected hosts and, thus, disease occurs - Opportunistic infections of HIV associated pathogens.
- T cells can be either permissive or non-permissive. What does this mean?
•Permissive T-cells allow replication unlike non-permissive cells (certain replication stages can’t be completed).
- What happens in permissive T cells?
In permissive cells, once the virus has replicated its genome into dsDNA. This DNA enters the nucleus and is recognised as non-self, this causes caspase-3 activation which triggers apoptosis (cell death).
o For the most part, the virus will shut down/evade this immune response to virus replication but some cells (small numbers) will die.
- What happens in non-permissive cells?
In non-permissive cells, full viral replication doesn’t occur however the viral RNA/DNA is detected as non-self by IFI6 DNA sensor. This activates the innate antiviral and inflammatory responses as well as inflammasome assembly (multiprotein complex that activates highly pro-inflammatory cytokines). This results in the activation of caspase-1 which results in pyroptosis (cell death and excretion of immune factors that results in more inflammation).
- What are the effects of pyroptosis ?
• HIV infection causes pyroptosis which release cellular contents and pro-inflammatory cytokines which causes inflammation. Inflammation brings new T-cells to infect and destroy in a positive feedback cycle.
- How is there HIV independant cell death ?
•HIV independent: Uninfected cells migrate into the area due to inflammatory factors and undergo cell death resulting in more inflammation.
- What is the effects of the death of immune cells?
•This constant activation (over-charges) causes immunodeficiency which makes you susceptible to opportunistic infection.
- What are some HIV associated pathogens?
give eg of a virus, bacteria,fungus and parasite?
- Virus: Herpes simplex virus (HSV) or Kaposi’s sarcoma herpesvirus (KSHV).
- Bacteria: Mycobacterium tuberculosis (TB) or Salmonella.
- Fungus: Candida or Cryptococcus neoformans.
- Parasite: Cryptosporidium or Toxoplasma gondii.
- What is AIDS?
• Reactivation of oral/genital/anal Herpes Simplex Virus and Human Herpes Virus 8 in Kaposi’s Sarcoma.
- What are the two possible routes of infection of AIDS?
primary infection and reactivation from latency.
- How can primary infection be resolved?
• Primary infection can be resolved (typically by immune suppression) - Infection moves to sites in the host that the immune system does not access where they stay latent (resides without replicating).
- Why would there be reactivation from latency?
•Reactivation from latency occurs upon immunodeficiency (no immune suppression to dampen the virus).
- Explain how HSV becomes latent and they gets reactivated?
- The virus replicates in the infected epithelial cells and then moves into the nervous system which has poor immunosurveillance due to most immune cells not crossing over the blood-brain barrier.
- The virus then moves along neurons into the CNS where it sits in latency until there is immunodeficiency.
- Normally, continuous immunosurveillance sends signals to the virus. When this signal is removed the virus is reactivated from latency and travels back to the infection site.
- What is KSHV ?
Kaposi’s sarcoma-associated herpesvirus
ie Oncogenesis of Kaposi’s Sarcoma (cancer/) associated with HIV and AIDs
- What is A celll(A type KSHV?
• A: Asymptomatic KSHV infection in a healthy individual:
o The virus infects cells produces KS progenitor cells which is known as de novo (primary) infection which can lead to latent infection e.g. in a B cell or a lytic immunogenic response (destroys immune cells).
o The latent infection can be reactivated to enter the lytic cycle in response to a cue e.g. a T cell.
o The immunogenic response can lead to reinfection.
- What is B cell KSHV?
• B: Viral Oncogenesis of AIDS-Kaposi’s sarcoma:
o Some types of B-cells are permissive, and some are non-permissive for oncogenesis.
o Re-activation from latency into the lytic cycle by cues such as inflammatory cytokines. Some of these cells become oncogenic and undergo uncontrolled cell division.
o During the uncontrolled division, an inflammatory reaction occurs in KS legions which produces more inflammatory cytokines etc for latent reactivation.
o ART (anti-retroviral therapy) stops HIV replication which stops the inflammatory response.
o Gancyclovir (direct acting anti-viral drug) prevents KSV replication in B cells and other cells.
- What are some viruses that cause cancer?
- Human papilloma viruses (HPVs) – Papilloma virus, circular dsDNA genome, skin cancer.
- Epstein-Barr virus (EBV) – Herpes virus, linear dsDNA genome, lymphoma.
- Hepatitis B virus (HBV) – Hepadnavirus, circular dsDNA genome, carcinoma.
- Hepatitis C virus (HCV) – Flavivirus, ssRNA genome, carcinoma.
- Human herpes virus 8 (HHV-8) - Herpes virus, linear dsDNA genome, lymphoma.
- Human T-lymphotrophic virus-1 (HTLV-1) – Retrovirus, RNA-DNA genome, leukemia/ lymphoma.
- Merkel cell polyomavirus (MCV) – Polyomavirus, dsDNA genome, carcinoma.
