Antiviral -Immuno Treatment – Flashcards

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Antiviral Agents
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Selectively inhibit viral replication without affecting the normal functions of the host cell. They inhibit the viral nucleic acid replication process. 

 

Remember, there are no broad-specturm antivirals 

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Viral infections that have antiviral agents
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Herpesvirus, influenza viruses, hepatitis B and C viruses, respiratory syncytial virus, and HIV
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Raltegravir
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binds to the CCR5 coreceptor of some HIV strains
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Rimantadine and Amantadine
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bind to the M2 protein of influenza A virus, which inhibit this ion pore in the virion envelope, thus preventing H+ ion influx and uncoating
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Enfuvirtide
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inhibits HIV viral fusion protein g 
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Ribavirin
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Alters cellular nucleotide pools, inhibits viral RNA synthesis and may cause lethal RNA mutation. 

 

It is used for severe RSV infections and in combination with (interferon) IFV-alpha for chronic hepatitis C virus (HCV) infections 

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Analogues of Nucleosides
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prevent DNA chain elongation after recognition of base pairing.

 

These drugs are activated by phosphorylation by cellular or viral kinases. 

 

Examples include many herpes simplex, VZV, cytomeglovirus, and HIV antivirals 

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Thymidine analogs
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Inhibit thymine biosynthesis or replace thymidine in DNA which leads to misreading of the DNA and mutations.

 

Examples include: Idoxuridine, Trifluorothymidine, fluorouriacil. 

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Foscarnet
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is a nonnucleoside nucleic and polymerase inhibitor that binds to and inhibits the DNA polymerase of all herpesviruses and the reverse transcriptase of HIV.
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Nonnucleoside HIV reverse transcriptase inhibitors (DNA from RNA)
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Examples: Vevirapine, delavirdine, efavirenz. These are used in combination therapy with various nucleoside analog inhibitors of that enzyme.
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Maraviroc
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inhibits HIV integrase, preventing HIV provirus formation
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Protease Inhibitors
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Saquinavir, indinavir, ritonavir, nelfinavir, amprenavir 

 

These inhibit the action of HIV protease; used in combination with AZT and a second nucloside analog as "cocktail" therapy in HIV 

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Neuraminidase Inhibitors
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oseltamivir and zanamivir 

 

They inhibit the neuraminidase (essential for viral attachment) of influenza A and B viruses; they may be used for prophylaxis as well as treatment. 

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Fomivirsen
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A mRNA Inhibitor. A synthetic oligonucleotide complementary to a sequence in CMV RNA (an antisense compound). It prevents transcription of early CMV genes. 

 

It is approved for intravitreal (inside the eye) therapy of CMV retinitis after other therapies have failed .

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Interferons (IFN)
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Are host-coded proteins or glycoproteins produced in and secreted from virus-infected cells in response to viral infection 

 

They are host specific. 

 

Three groups recognized: IFN- alpha, beta, and gamma 

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IFN- alpha (Intron - A)
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licensed for treatment of chronic HBV and HCV infections and can produce adverse effects at high doses or with chronic therapy. These side effects include bone marrow suppression.
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Laboratory Viral Diagnosis
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Involves: 

1. Virus isolation

2. Direct demonstration of the virus, viral nucleic acid, or antigens in clinical specimens

3. Serologic testing of viral specific antibodies 

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Virus Isolation
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Identifies virus replication in susceptible cells . Embryonated eggs or animal hosts often used. 


a. in live infected tissue culture cells, replication may be detected by observing a cytopathogenic effect, polykaryocyte formation or hemadsorption. 

 

b. fixed infected tissue culture cells. Replication may be detected by observing characteristic inclusion bodies (in nucleus or cytoplasm)...deposit of protein or carbs left behind.  

 

 

C. In embryonated egg, replication is detected by pock formation. In animals, by the development of clinical symptoms 

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Direct examination of clinical specimens
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samples include tissue biopsies, smears, CSFs, urine, etc

 

Examples of assays: immunohistochemical staining, nucleic acid hybridization, amplification methods

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Direct examination of clinical Specimens: Nucleic acid hybridization and amplification
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highly sensitive and specific. detects viral DNA or RNA . PCR may be used to amplify viral genes; Dot Blot hybridization techniques that usually use ss complementary nucleic acid probes
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Direct-phase immunoassays: Solid phase Immunoassays
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Detect antigens such as rotavirus and HAV 

 

They use specific viral Abs and radioimmunoassay or enzyme-linked immunosorbent assay. 

 

These assays are highly sensitive and speficic 

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Serologic Tests
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Used to determine the titer of specific antiviral Abs. 

 

Paired blood samples are taken. At least a 4fold increase in titer between the samples must be present to indicate a current infection. 

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Serologic test: Virus neutralization test
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based on the fact certain Abs will neutralize the cytopathic effect of the virus.

 

If cytopathic effect neutralized by a particular serum: the sample is positive and Abs in the serum were effective against the virus and visaversa. 

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Serologic Tests: Hemagglutination inhibition tests
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based on the idea that serum with inhibit viral agglutination of erythrocytes. 

 

Tests can only be done with viruses that have hemagglutinins on their surface (influenza, measles) 

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Serologic Test: Solid-phase immunoassays
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Used to detect specific viral Abs. Use RIA and ELISA protocols. several 100xs more sensitive than other serologic tests
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Passive Immunization
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injection of human plasma or gamma-globulin fractions from immune individuals 

 

Used to prevent: rubella, measles, mumps, HAV, HBV, rabies, and Varicella-zoster virus (VZV)

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DNA vaccines
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Plasmid DNA expressing vectors that elicit both humoral nad cell-mediated immune responses. 

 

Used for HIV and influenza 

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Viral polypeptides
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Sequences of virion receptors that have been 

 

Advantages and disadvantages are the same for killed vaccines 

 

Ex: HBV, HEV (hep. E virus) , HPV (human papillomavirus)

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Virion Subunit Vaccines
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purified proteins (viral receptors) obtained from virions. 

 

Advantages and disadvantages are the same as for killed vaccines

 

Ex: adenovirus 

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Killed Virus Vaccines
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Prepared by heat or chemical inactivation 

 

Advantage: easily combined into vaccines. Doesn't elicit an immune response

 

Disadvantage: lack of development of secretory IgA. You need boosters; poor cell-mediated response

 

Examples: poliovirus, rabies, influenza, HAV

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Live Virus Vaccines
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Attenuated strains that are avirulent

 

Advantage: admin. in single dose; induces wide spectrum of Abs and cytotoxic cells 

 

Disadvantages: limited shelf life, possible reversion to virulence, possible production of persistent infection

 

Ex: measles. mumps, rubella, chickenpox, rotavirus, yellow fever, some adenovirus strains

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Viral induced Immunopathology
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Rxns (immediate hypersensitivity, antibody-antigen complexes) can contribute to a disease process and are a common feature of persistent viral infections 
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Cell-mediated Immunity
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Involves cytotoxic T lymps., Ab-dependent cell-mediated cytotoxicity, NKcells and activated macrophages. 

 

This is the most important defense mechanism against noncytolytic infection (alteration of the virus-infected cell membrane)

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Humoral Immunity
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Production of B lymphs. of neutralizing and nonneutralizing Abs against viral-specific antigens. This is the most important against cytolytic viral infections
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Neutralizing Abs
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Part of the Humoral Immune system: inhibit the ability of a virus to replicate by inhibiting viral attachment, penetration, uncoating, or all 3 processes .

 

Lesions may also be induced in the viral envelope with the aid of a complement 

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Nonneutralizing antibodies
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Part of Humoral immunity: enhance phagocytosis of virions by acting as opsonins.
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Interfering RNA (RNAi)
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Process: 

1. ds viral RNA interacts with host ribonuclease DICER

2. Forms short interfering RNAs (siRNAs) which interact with argonaute proteins to form RICS (RNA-inducing silencing complexes)

3. RISC binds to viral mRNA and inhibits viral gene expression 

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Nonimmune Defenses
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1. Innate immunity : anatomical and chemical barriers 

2. Cellular resistance

3. Inflammation: creates low pH, elevated temp. 

4. IFN: inhibits viral replication; species specific; the first viral induced defense mech. 

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