Viral Pathogenes; Classification, Biology, Diseases II Flashcards
How does a typical untreated HIV patient deal with the infection?
In a typical untreated patient, ten billion virions are made and destroyed every day during the chronic phase of disease
Describe the relationship between T cells and viral RNA as infection progresses
As infection continues CD4 T cells decrease but viral RNA increases
What causes immunodeficiency in HIV Infection?
The inexorable depletion of CD4 T cells during infection ultimately leads to immunodeficiency (AIDS) and mortality (via opportunistic infections)
How does the immune response hinder HIV infection?
Viruses must evade immune responses; mediated by specific cells that recognize and kill virally infected cells
How do viruses evade the immune response?
Some viruses replicate in the immune cells whose function is to recognize and kill infected cells
How does replicating in immune cells evade the immune response?
Replication in immune cells hides the virus from immune cells and inhibits immune cell function
What is the consequence of immune cell function inhibition?
Inhibition of immune cell function allows other pathogens to replicate in virus infected hosts
> Opportunistic infections of HIV associated pathogens
What are the 2 types of advantageous T cells to HIV?
- Non-permissive CD4 T-cell; cannot replicate fully
- Permissive CD4 T-cell; virus can replicate
How does HIV replication differ among different T cells?
HIV can get into both kinds of T cells but will replicate properly only in permissive T-cells
Both types have disadvantageous components to HIV
Outline the disadvantage to HIV of replicating in CD4 T cells?
The nucleus is a tightly regulated organelle; any foreign DNA is recognised and there are mechanisms in order to remove it via apoptosis due to caspase 3 activation - immune response
How do permissive T cells overcome the disadvantageous immune response to HIV?
In the permissive cell, HIV polyproteins (Vyf, Nyf, VPR) can deactivate apoptosis activation - doesn’t always occur
Outline how the immune response against HIV can be deleterious towards other healthy cells
- HIV infection
- Apoptosis causes cell death
- Release of proinflammatory cytokines and cellular
contents - Inflammation; recruits more CD4 T-cells
- Positive feedback mechanism; more CD4 T cells =
more HIV infection
How does HIV infection cause immunodeficiency?
Inflammatory immune response hyper charges the immune system causing neutrophil & monocyte migration to unaffected cells ⇒ increased inflammation and exhaustion of immune response - immunodeficiency
What are the viral HIV associated pathogens?
- Herpes simplex virus (HSV)
- Kaposi’s sarcoma herpesvirus (KSHV)
Name the fungi HIV associated pathogens?
- Candida
- Cryptococcus neoformans
Give examples of the parasite HIV associated pathogens
- Cryptosporidium
- Toxoplasma gondii
What are the bacterial HIV associated pathogens?
- Mycobacterium tuberculosis
- Salmonella
What condition is a result of unchecked HIV?
Large number of unchecked HIV infections (e.g. KSHV; kaposi sarcoma herpes virus) colonises and infect its host
What is the consequence of KSHV?
Sarcoma lesions unchecked can lead to metastatic sarcoma disease; systemic infection → neuronal damage - painful and rapid mortality
What are the 2 methods of viral associated HIV Pathogen infections?
Two possible routes of infection
- primary infection
- reactivation from latency
How does primary infection become latent?
Primary infection resolved (typically by immune suppression) and infection moves to sites in host that immune system doesn’t access
In these sites the virus resides without replicating: latency
What causes KSHV reactivation from latency?
Reactivation from latency occurs upon immunodeficiency
Outline how KSHV infection is reactivated form latency
- HSV exposure through skin; epithelial cell infection
- Viral replication in host cell and then moves into nervous system
- Moves into dendrites and CNS
- Immune regulation sends signals to latent infections
- When immune signal is no longer present (immunodeficiency), virus reactivates from latency and travels back to site of infection ⇒ productive infection
Where does productive infection occur (reactivated from latency)?
Productive infection can occur in the cell of infection origin or neighbouring cells
Where do latent infections commonly reside?
Nervous system as it has poor immune regulation due to the fact immune cells don’t cross Blood brain barrier
Why does KSHV infection not reactivate from latency before immune deficiency?
As KSHV infects B cells it interferes with B cell - T cell interactions that would normally occur
Due to lack of interaction between immune cells there is no impotence for virus to reactivate from latency
What mechanism induces reactivation of KSHV from latency
In HIV sufferers, there is a lack of T cells ∴ a lack of immune signals indicating no B-T cell interaction
This causes reactivation to occur
Outline how reactivation of KSHV can lead to cancer
- Virus is replicating at a very low level / not at all
- Cellular/viral cue occurs; inflammatory cytokines
- Reactivation from latency
- Lytic, productive, cytopathic, immunogenic effects
occur from virus production - Reinfection of new cells
- Some B cells become oncogenic - uncontrolled cell
division
Why does KSHV not develop into cancer in all infection cases?
KSHV only occurs in very specific (cancer) circumstances;
- Just like HIV some B cells are permissive / non-permissive
- Thought that B cell morphology is altered to allow cancer to form
How do lesions induce production of oncogenic cells in KSHV?
KS lesions cause a positive feedback mechanism as more B cells undergo transformation into oncogenic cells
How is KSHV treated?
- ART (antiretroviral therapy) stops HIV infection and inflammatory response
- Ganciclovir direct acting antiviral drug prevents replication of KSHV in B cells
