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Lecture 12

MICB 202 Lecture Notes - Lecture 12: Simian Immunodeficiency Virus, Chemokine Receptor, Reverse TranscriptasePremium

12 pages40 viewsSummer 2017

Department
Microbiology
Course Code
MICB 202
Professor
Tracy Kion
Lecture
12

This preview shows pages 1-3. to view the full 12 pages of the document.
Topic 4: Retroviruses case study
Human Immunodeficiency Virus (HIV)
- virus that can lead to AIDS
- sugoup Letiiuses, o slo iuses
- long interval between initial infection and onset of serious symptoms
- mutation in simian immunodeficiency virus (SIV) when transmitted from chimpanzee
to humans during contact with the infected blood
HIV-1 form that is primarily circulating in North America
HIV-2 originally isolated from AIDS patients in West Africa; has the same modes of
transmission as HIV-1 and is associated with similar opportunistic infections and AIDS
Both types daage a peso’s iue syste y destoyig the CD4+ T cells (crucial to
adaptive immune responses).
HIV-1 Groups
- four groups: M, N, O and P
- each group is a result of an independent transmission of SIV into humans
- Group M can be subdivided into subtypes (clades) based on genetic sequence data
(A, B, C, D, F, G, H, J, K, CRFs)
- some clades are more virulent or are resistant to anti-retroviral drugs
- Group M subtypes predominate and are responsible for AIDS pandemic
Acquired Immunodeficiency Syndrome (AIDS)
- final stage of HIV infection
- diagnosed when an HIV+ person has one of more opportunistic infections (or certain
cancers) and a CD4+ T cell count of less than 200 cells per l of blood
Acquired: disease that develops after birth from contact with a disease-causing agent (not
hereditary) i.e. HIV
Immunodeficiency: disease is characterized by a weakening of the immune system
Syndrome: a group of symptoms that indicate or characterize a disease
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Transmission of HIV
When HIV enters the body via the mucosal route (epithelia of the vagina, penis or rectum),
macrophages and dendritic cells at the mucosal surface can be infected with the virus.
Recall: macrophages and dendritic cells also express the CD4 protein
Sexual contact
Injection drug use
Pregnancy, childbirth & breast feeding
Occupational exposure
Blood transfusion/Organ transplant
Host cell range
- HIV can infect multiple cell types in the human body, including brain cells
- Main target: CD4 T cell
- Requires a receptor (CD4) and a co-receptor (CCR5 or CXCR4)
- CCR5 and CXCR4 are chemokine receptors
- HIV can infect macrophages and dendritic cells since they express CD4
- HIV-infected macrophages secrete chemokines attract CD4 T cells to infection site,
recruiting more primary target cells
- Dendritic cells trap HIV on their surfaces; they possess a surface lectin (DC-SIGN) that
binds to the HIV gp120
- DC-SIGN also participates in association of dendritic cells with CD4 T cells
Discovery of HIV co-receptor for entry
T cells isolated from mice that expressed the human form of CD4 could not be
infected with HIV suggested that something else was required
Individual that were repeated exposed to HIV, yet remained seronegative, had
unusually high concentration of chemokines in their blood
Chemokine receptors
Serpentine 7 transmembrane-spanning domain structure
Extracellular portions involved in chemokine binding
Intracellular portions involved in cell signaling
Some have a role in infectious disease susceptibility or pathogenesis
Co-receptors
In peripheral blood, T cells and monocytes express CXCR4 and CCR5.
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CXCR4 (X4 strains) tend to infect predominantly T cells
CCR5 (R5 strains) infect both T cell and monocytes
- R5 viruses appear early in infection; responsible for virus transmission
- X4 strains appear late; associated to faster decline of CD4+ T cells
Clade B isolates predominate in North American and Western Europe
CCR5-Δ mutation in the CCR5 gene (32 bp deletion, frame shift)
highly resistant to HIV infection (but not absolute)
present in 2% of the Caucasian population
If the person is homozygous for CCR5-Δ, the resistance might result from
- genetic loss of CCR5 on the cell surface
- active down-regulation of CXCR4 expression by the mutant CCR5-Δ protein
Clinical features of HIV infection
Some symptoms are developed a few days or weeks after infection occurs
Can be describe in 3 stages
Measured by CD4 T cell counts and HIV viral load (virus in the blood)
1. Acute infection
- large amounts of the virus are being produced in the body
- most people develop flu-like syptos desied as the ost flu ee
2. Clinical latency
- HIV reproduces at very low levels (still active)
- may not have symptoms
- people may live with clinical latency for several decades with proper HIV treatment
- without treatment, it lasts for 10 years, but some may progress through faster
3. AIDS
- CD4 cells fall below 200 cells/mm2
- Without treatment, people typically survive 3 years
Acute HIV infection
Rapid viral replication abundance of virus particles in blood, decline in circulating
CD4+ T cells
Non-specific symptoms of infection (some experience no symptoms at all)
Fever, headache, fatigue, swollen glands (lymph nodes), sore throat, nausea,
vomiting, diarrhea, joint pain and muscle aches, skin rash, night sweats
Symptoms may last for several days or weeks
often misdiagnosed as Influenza
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