Virsuses: Human Immunodeficiency Syndrome & Acquired Immunodeficiency Syndrome
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Transcript of Virsuses: Human Immunodeficiency Syndrome & Acquired Immunodeficiency Syndrome
Virsuses:Human Immunodeficiency Syndrome
& Acquired Immunodeficiency
Syndrome
Outlinewe may need to save some topic in lecture
• Origins of HIV based on scientific evidence• HIV viral particle• Mechanism of infection• Transmission• Treatment• AIDS• Prevention• Clinical Detection and Diagnosis
Greater spot nose monkey Red capped mangabey monkey
SIV cpz almost identical to HIV 1
Humans
Pan troglodytes troglodytes
Simian Virus (SIV cpz) almost identical to HIV 1
Sooty mangabey monkey
Simian Virus corresponds to HIV2
HIV: Structure and mechanism of replication
HIV
HIV-1 PARTICLE
The key HIV genes
Mechanism of Infection
VIRAL RNA
PROVIRAL DNA
Infects Th cell
Integrates into host DNA
“activated”LYTIC STAGE storage
LYSOGENIC STAGE
RETROVIRAL REPLICATION
HIV animations
http://search.live.com/video/results.aspx?q=HIV+animation&docid=1601834254601#docid=1601834254601
http://search.live.com/video/results.aspx?q=HIV+animation&docid=1601834254601#docid=1669495456158
http://www.hivinfosource.org/hivis/hivbasics/animations/index.html
T lymphocyte in green and HIV in red
HIV and helper T cells
HIV-1
HOST CELLS: helper T lymphocyte, macrophages
LYTIC STAGE
Transmission of HIV
Transmission of HIV
• Biological fluids
– Blood– Sexual transmission (Semen)– Breast milk– Transplant tissues
Non-transmitting sources of HIV
• Tears
• Saliva
• Mosquito or insects
• Swimming pool
• Food handling
Highly Active Antiretroviral Therapy (HAART)
Cocktail Therapy
Examples of anti-retroviral drugs
• Cocktail Drug Mixtures
– Protease inhibitors
– Non-nucleoside RT Inhibitors (NNRTIs)
– Nuleoside/nucleotide RT inhibitors (NRTIs)
– * Fusion Inhibitors *Fuzeon
– Integrase Inhibitors
Fusion Inhibitors block
• Co-receptors on host cell
• Gp120/gp 41 on viral particle
or
Co-Receptors
CCR5 or CXCR4 (fusin)
Binds naturally occurring chemokines
Prevention
• Condoms
• Clean needles
• Treatment of pregnant mother with anti-viral drugs
• Blood screening
• Abstinence
Acquired Immunodeficiency Disease
Symptoms of AIDS
• Decrease T cell count
• Rapid weight loss
• Recurring fever and dry cough
• Profound fatigue
• Swollen lymph glands
Symptoms of AIDS
• Persistent diarrhea
• Unusual blemishes on the tongue, mouth, or throat
• pneumonia
• memory loss, depression
Acquired Immunodeficiency Syndrome
Opportunistic Diseases and cancer
• pneumonia
• Kaposi’s Sarcoma Kaposi’s Sarcoma
HIV Diagnostic Tests
• ELISA
Indirect evidence of HIV exposure
measu
res
HIV Diagnostic Tests
• Western Blot
• PCRDirectly measures HIV
Polymerase Chain Reaction• Measures proviral DNA within the host DNA
Western BlotIdentifies HIV proteins
Protein ladder
• A diagnostic test for Antibodies to HIV
Enzyme Linked Immunosorbent Assay
(ELISA)
Antibodies
Antibodies are proteins produced by our immune system that are directed
against specific antigens.
Antibodies Antigens
Immune system Non-self
Now apply these concepts to the diagnostic test known as ELISA to detect antibodies against HIV from a biologic
fluid.
Do any of these individuals carry antibodies to HIV?
ELISA MICROTITER PLATES
Microtiter plate
The ELISA protocol
1
23
4
antigen
sampleLabelled 2nd Ab
Color inducing substrate
Results
POSITIVE ANTI-HIVCOLOR CHANGE
NEGATIVE ANTI-HIVNO COLOR CHANGE
FDA Approves Saliva OraQuick Rapid Test for HIV-1, HIV-2
Antibodies[March 29, 2004]
(similar test is also available for blood samples, see next slides).
OraQuick Rapid Anti-HIV Blood Test
1 2
3 20 minute testCost app. $15.00
Onto the ELISA lab
For Your Information and Files
Acquired Immunodeficiency Syndrome
• Normal CD4+ count
• Normal CD4+ (%)
• AIDS
• 500-1600/mm3
• 20-40%
• <350/mm3 begin anti-viral treatment
• <14% serious immune damage
Table 1. For Your personal Information: not for lecture.Antiretroviral Agents
Agent Type Dose Major Toxicities
AZT NRTI 300 mg bid nausea, headache, low blood counts
ddI NRTI 125-200 mg bid or 250-400 mg qd(tablet form)
diarrhea, pancreatitis, peripheral neuropathy
ddC NRTI 0.750 mg tid diarrhea, peripheral neuropathy
d4T NRTI 30-40 mg bid abnormal liver function tests,peripheral neuropathy
3TC NRTI 150 mg bid minor
abacavir NRTI 300 mg bid hypersensitivity reaction
tenofovirNRTI (nucleotide)
300 mg qdnausea, diarrhea, vomiting, flatulence
AZT/3TC (Combivir)
NRTI one pill bid(300 mg AZT/150 mg 3TC)
see above
AZT/3TC/abacavir(Trizivir)
NRTI one pill bid(300 mg AZT/150 mg 3TC/300 mg abacavir)
see above
nevirapine NNRTI 200 mg bid rash
delavirdine NNRTI 400 mg tid rash
efavirenz NNRTI 600 mg qhs rash, dizziness, impaired concentration, insomnia, abnormal dreams
saquinavir(Fortovase)
PI 1200 mg tid diarrhea
ritonavir PI 600 mg bid nausea/vomiting, drug interactions
indinavir PI 800 mg tid kidney stones
nelfinavir PI 750 mg tid or 1250 mg bid
diarrhea
amprenavir PI 1200 mg bidnausea/vomiting, diarrhea, rash
lopinavir/ritonavir
PI three capsules bid(133.3 mg lopinavir/33.3 mg ritonavir)
diarrhea, nausea, weakness, headache
Experimental drugs are italicized, and approved drugs are in regular, non-italicized type)
Brand NameGeneric Name Abbreviation Experimental Code Pharmaceutical Company
Fuzeon™ enfuvirtide ENF T-20 Trimeris and Hoffmann-La Roche
BMS-488043 Bristol-Myers Squibb
GSK-873,140 GlaxoSmithKline
PRO-542 Progenics Pharmaceuticals
SCH-D Schering-Plough Corporation
TNX-355 Tanox and Biogen Idec
UK-427,857 Pfizer
Interesting links on HIV
• http://www.niaid.nih.gov/factsheets/aidsstat.htm– Links to global and US HIV/AIDS statistics
• http://www.avert.org/pregnanc.htm– Links to HIV and pregnancy as well as numerous other links
including statistics on global epidemic; HIV/AIDS quizzes and treatment.
• http://www.cdc.gov/hiv/pubs/facts/transmission.htm– Links to CDC and a comprehensive fact sheet on HIV transmission
Experimental drugs are italicized, and approved drugs are in regular, non-italicized type) Brand NameGeneric NameAbbreviationExperimental Code Pharmaceutical Company Fuzeon™enfuvirtideENFT-20Trimeris and Hoffmann-La Roche BMS-488043Bristol-Myers Squibb GSK-873,140GlaxoSmithKline PRO-542Progenics Pharmaceuticals SCH-DSchering-Plough Corporation TNX-355Tanox and Biogen Idec UK-427,857Pfizer What are Entry Inhibitors (including Fusion Inhibitors)?Entry inhibitors work by preventing HIV from entering healthy T-cells in the body. They work differently than many of the approved anti-HIV drugs – the protease inhibitors (PIs), the nucleoside reverse transcriptase inhibitors (NRTIs), and the non-nucleoside reverse transcriptase inhibitors (NNRTIs) – which are active against HIV after it has infected a T-cell. Entry inhibitors work by attaching themselves to proteins on the surface of T-cells or proteins on the surface of HIV. In order for HIV to bind to T-cells, the proteins on HIV's outer coat must bind to the proteins on the surface of T-cells. Entry inhibitors prevent this from happening. Some entry inhibitors target the gp120 or gp41 proteins on HIV's surface. Some entry inhibitors target the CD4 protein or the CCR5 or CXCR4 receptors on a T-cell's surface. If entry inhibitors are successful in blocking these proteins, HIV is unable to bind to the surface of T-cells and gain entry into the cells. Only one entry inhibitor has been approved by the U.S. Food and Drug Administration (FDA): Fuzeon™ (T-20). This drug targets the gp41 protein on HIV's surface. Some experimental drugs target proteins on T-cells: BMS-488043 targets the gp120 protein, PRO-542 and TNX-355 target the CD4 protein, and SCH-D, GSK-873,140 and UK-427,857 target the CCR5 protein. HIV-positive people who have become resistant to PIs, NRTIs, and NNRTIs will likely benefit from the entry inhibitors because they are a different class of drugs. This is good news for HIV-positive people who have tried and failed many of the currently approved anti-HIV medications.To learn more on how HIV infects a T-cell and begins to create more viruses, and where each class of anti-HIV drugs blocks this process, click on the following lesson link:
The HIV Life Cycle (and the targets of each class of anti-HIV drugs)