Virology I - Mclean Flashcards
Nonenveloped virus vs Enveloped virus
Where is protein envelope from?
Nonenveloped virus only contains a capsid and nucleic acid.
Enveloped virus contains these and also an envelope, which consists of proteins in envelope membrane. This is from the HOST CELL
how to get protein from ssRNA.
ssRNA -> + polarity / strand -> mRNA sense -> protein synthesis
ssRNA -> - polarity / strand -> anti mRNA sense
if its -, you have to convert it to + to get protein.
protomer vs capsomere.
helical vs icosahedral
protomer is a monomer of a capsomere.
protomer = single polypeptide type. Helical made of protomers
capsomere = group of protomers. Icosahedral made of capsomeres.
One-step growth curve
eclipse period
exponential growth.
1 virus infects cell. You have eclipse period, where virus disassembles. You then have reassembly, and this is where eclipse period ends.
eclipse period: time from initial entry to assembly of first progeny virion. VIRUS = NONINFECTIOUS
exponential growth: rapid progeny production after eclipse period.
Steps in Replication Cycle:
Step 1: Adhere. (stick to) Binds to surface of cells via normal receptors
2.) Penetrate
3.) Uncoat (take out nucleic acid)
4.) Replication of viral genome
5.) Assembly, release of viral genome.
2 principal mechanisms of penetration:
Receptor-mediated endocytosis. (invagination of membrane)
Membrane fusion. (Envelope virus). Membranes fuse from both host cell / virus
Location of Viral genome in cell:
Most DNA viruses tend to replicate in the nucleus.
Most RNA viruses tend to replicate in the cytoplasm or cytosol.
Replication of Viral Genome:
DNA virus replication mechanism
Parental DNA -> Early mRNA -> Early Proteins.
Early Protieins -> replication of virus. Makes progeny DNA.
Progeny DNA -> late mRNA -> Late proteins.
Early proteins play important role in replication.
Late Proteins play important role in assembly of nucleocapsids.
Replication of Viral Genome:
RNA virus replication mechanism
+ ssRNA -> Viral proteins.
Viral proteins include RNA-dependant RNA polymerase
which convert the + ssRNA to -ssRNA.
-ssRNA goes through another round from RNA-dependant RNA polymerase to make +ssRNA.
From -ssRNA, virus caries in a premade RNA-dependent RNA polymerase (enzyme) into the host so it can do this.
Release of progeny viruses
Enveloped vs naked:
Enveloped typically released via budding
Naked typically released via lysis
Episome:
Nucleic acid from virus hangs out separate from host cell, like a plasmid.
Response of a host cell to viral infection ranges from:
1.) Viral infections in which no progeny virus produced (nonpermissive cells) (nothing happens)
2.) Viral infections which host cell surface altered antigenically but not killed, progeny released (budding)
3.) Viral infections result in a latent viral state in host cell. Persistence of viral genome inside host genome, latent viruses. (fuse with DNA, example is HIV)
4.) Lysis
CCR 5 Delta 32:
Mutation CC, mutates receptor on cell that HIV normally binds to.
Retroviridae (HIV):
General Characteristics
skim
Lipid envelope
+ ssRNA
Linear RNA (2 identical copies)
Icosahedral capsid
3-9 genes
Genus of HIV:
Lentivirus
SIV and FIV are also lentiviruses
3 important genes for HIV
gag: Group Associated antiGens
pol: POLymerase (RNA-dependent DNA polymerase or reverse transcriptase), integrase, and protease
env: ENVelope glycoproteins (gp120 - surface protein attachment, gp41 - transmembrane protein)
Also has poly A tail which provides stability
One way to look for HIV:
(diagnosis)
Look for CA = Major capsid protein (p24)
HIV Cell Tropism (which cells do they like to infect?)
CD4 T cells.
Macrophages/Monocytes. Major reservoir cell
how HIV binds to cell:
gp41 - gp120 complex
gp120 part binds to CD4
gp120 associates with CCR 5. CCR5 is an important secondary receptor.
gp41 then associates with membrane. Entry is via fusion, mediated by gp41.
Replication of HIV:
1.) Virus attachment, fusion of viral envelope
2.) +ssRNA goes to dsDNA
3.) dsDNA integrates into host DNA
4.) can make viral +ssRNA again and thus make viral proteins.
provirus term:
pro virus is generally a term where viral DNA gets incorporated into your DNA.
When it’s inside your DNA, we tend to call it a pro virus.
When not inside, it is called an episome.
When do you have Aids
<200/uL = AIDS
(CD4 T cell count)
Viral Infections of AIDS:
U get a lot of things, but important are malignancies:
Kaposi’s sarcomma. Caused by Herpes virus 8
Spectrum of Immune dysfunction:
Lymphopenia (decreased CD4 T cells)
Decreased Cytotoxicity (Tc, NK cells)
Decreased monocyte/macrophage function
Skin anergy (absence of normal immune response to antigens)
Treatment for HIV
Reverse transcriptase inhibitors.
AZT (Azidothymidine, Retrovir, Zidovudine) - 1987
This significantly decreases risk of mother-to-fetus transmission
HAART:
important***
Highly Active Anti-Retroviral Therapy
3 drug combinations
- from at least 2 classes of antiretrovirals
Antiretrovirals:
1.) Entry inhibitors
2.) NRTI (typically 2 from this class)
3.) NNRTI
4.) Integrase inhibitors
5.) Protease inhibitors
If you only target one site, drug might not be affective.
Drug you can take to reduce risk of infection:
Truvada
The Herpes Viruses:
KNOW ALL NAMES: 1-9
Herpes Simplex Virus-type1 (HSV1): Human herpesvirus 1
Herpes simplex virus-type 2 (HSV2): Human herpesvirus 2
Varicella-Zoster virus (V-Z): Human herpesvirus 3
Epstein-Barr virus: Human Herpesvirus 4
Cytomegalovirus (CMV): Human Herpesvirus 5
Human herpesvirus 6: Human Herpesvirus 6
Human herpesvirus 7: Human Herpesvirus 7
Kaposi’s sarcoma-herpesvirus: Human Herpesvirus 8
Structure / Composition of Herpes:
Large
Icosahedral capsid
Lipid Envelope
One molecule of linear dsDNA
Contains Tegument: Protein material covering viral enzymes
Difference between incubation period and Window period:
Incubation period: time between infection and symptoms
Window Period: Time between infection and positive test.
Pathogenesis of HSV
virus -> mucosal surfaces / broken skin -> virus replicates in nucleus -> invades nerves, spreads to ganglia -> latency
Can then come back and reactivate after hanging out in the ganglia.
HSV-1 facts:
clinical findings
Oropharyngeal disease, common in children
occasionally in genitals
can infect mouth (herpes Labialis), throat, genitals, brain (highly fatal), eye (HSV Kerato-conjunctivitis), lip, finger (whitlow)**
Eczema Herpeticum: promotes infection on skin
HSV-2:
way more painful, affects genital herpes. occasionally in oral areal
neonatal herpes
Latency site of HSV1 and 2
HSV1 - trigeminal ganglia (oral)
HSV2 - Sacral ganglia (genital)
When are kids susceptible to HSV1
months 6 - 2 years
lack antigens
dont let ppl kiss ur babies
honey also bad cuz of botulinum toxin
Treatment of HSV
classic question***
Acyclovir (acycloguanosine) It is a GUANOSINE analog, compared to AZT which is a THYMIDINE analog.
Valacyclovir is a prodrug of acyclovir (same as aciclovir)
3’ OH missing on both
Mechanism: Competitively binds to and inhibits viral DNA polymerase
Varicella-Zoster Virus (Chickenpox and Shingles)
V-Z is one virus.
similar to HXV
Linear dsDNA
Enveloped
Icosahedral symmetry
Transmission:
Respiratory droplets
Shingles vs chickenpox
clinical findings:
Varicella (chickenpox): rash, generalized, little to no pain. (younger age)
Zoster (Shingles): Rash, unilateral (concentrated in one area), intense pain. (older age)
Reye Syndrome:
Classic Question***
If you have chickenpox / influenza, do not take aspirin. Associated with development of brain disease. (encephalopathy)
Treatment of V-Z
Acyclovir, if severe
Epstein-Barr Virus:
important facts about it
Associated with malignancy. - can have B-cell lymphoma
*Can be transmitted via saliva. termed “kissing disease” *
THINK of B-cells being infected.
IgM class contains HETEROPHILE ANTIBODIES. These react with other species antigens. IgM class.
Make atypical lymphocytes (large lymphocytes)
clinical findings of Epstein-barr virus:
Splenomegaly.
Spleen can become enlarged, due to lymphoid tissue affected. Avoid physical activity (contact sports)
Epstein-barr virus:
laboratory diagnosis:
*** important classic question
Can look for heterophile antibodies via Monospot test.
Cytomegalovirus (CMV)
potential question
Infected cells swollen (very large), multinucleated, sticking together.
- Is the most common cause of intrauterine infections and congenital abnormalities in the US.*
NO acyclivir treatment for this one
Human Herpes Virus 6-7
Target question:
Causes Roseola Infantum
Transient rash (1-2 days) that occurs after a fever of about 3 days duration.
High fever (3 days) -> Rash (1-2 days)
Human Herpes Virus 8:
Kaposi’s sarcomma: cancer that develops from cells lining lymphatic and blood vessels. Most common AIDS associated neoplasm
Oral region related stuff(final):
HSV-1: major site: oral cavity
Kaposi’s sarcoma (Herpes-8): can hit oral cavity, tumor
Acyclovir: drug of choice for treating herpes. GUANOSINE analog. 3’ OH missing so u cant extend molecule.
