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101 Cards in this Set

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General characteristics of Herpesvirus
Enveloped

Icosahedral capsid

dsDNA

Pleomorphic

Replicates in cell's nucleus

Encodes own DNA polymerase and Thymidine Kinase

Latency Associated Transcripts
What type of genome does Herpesvirus have?
dsDNA
What is the shape of Herpesvirus capsid?
Icosahedral
Is Herpesvirus enveloped or naked?
Enveloped
WHere does Herpesvirus replicate?
Viral dsDNA

Replicates in nucleus

Has its own DNA polymerase and thymidine kinase
What machinery is needed for Herpesvirus to replicate?
Must replicate in cell's nucleus

Encodes its own DNA polumerase and thymidine kinase

Necessary to replicate in cells where replication is not occurring (neurons)
What happens to the cell following the release of Herpesvirus?
Cell lysis

No budding involved
Latency Associated Transcripts
LAT

Viral genes that are expressed during the latency period of Herpesvirus

It maintains the latent state and helps bring virus out later
How does Herpesvirus avoid immune response?
1. Direct cell-to-cell spread, so no viremia, preventing antibody attack

2. Mimics IL-10 to suppress IFN response

3. Blocks MHC presentation preventing cell-mediated immunity by T-cells

4. Becomes latent so no viral proteins are made
How is Herpes Simplex Viruses spread?
Spread via Direct Contact

Mucosa to mucosa
or
Childbirth (HSV-2)
Which Herpes Simplex Viruses predominately gets transferred during childbirth?
HSV-2

50% mortality
45% cognitive impairments
5% normal
Where does HSV-1 present?
Associated with oral infections

But 15% cross-over of HSV-2
Where does HSV-2 present?
Associated with genital infections

But 15% cross-over of HSV-1
How does Herpes Simplex Viruses avoid Immune response?
1. Cell-to-cell spread prevents verimia and antibody detection

2. Forms syncytia to help cell-to-cell spread

3. Establishes latency in neurons
Where does HSV-1 establish latency?
Sensory Neuron (Trigeminal Ganglion)
Where does HSV-2 establish latency?
Sacral/Lumbar Neuron
What causes Herpes Simplex Virus to reactivate from latency?
Stress
immune suppression
Menstruation
UV light
Temperature changes
Where does Herpes Simplex Virus derive their envelope following replication and assembly?
Derived from nuclear membrane, not lipid bilayer
What are some clinical diseases of HSV?
Herpes Labialis

Herpes Whitlow

Eczema Herpeticum

Keratoconjunctivitis

Encephalitis

Primary Herpetic Gingivostomatitis
Herpes Labialis
Caused by HSV (mainly HSV-1)

Cold sores
Herpes Whitlow
Infection on the skin from HSV

Usually due to infection through open wound from the saliva of patients
Prevention for HSV
No vaccine

Avoid contact with lesions
Treatment for HSV
Acyclovir - Guanosine analog that targets thymidine kinase

Becomes incorporated into viral genome stopping DNA synthesis because it terminates the chain

Only active in infected cells
Acyclovir
Treatment for HSV and VZV (Varicella Zoster Virus)

Guanosine analog

Converted to GMP by thymidine kinase
Converted to GTP by cellular kinase
Becomes incorporated into viral genome
Stops DNA synthesis because new nucleotides cannot be added

CHAIN TERMINATOR

Works only on active infected cells (not latent ones)
How does Varicella Zoster Virus spread?
Spreads person-to-person by COUGHING/SNEEZING

Only Herpesvirus that transmits this way
Where does VZV remain latent?
Dorsal root ganglia
What is the clinical manifestation of VZV?
Chicken pox

Shingles
When causes VZV to reactivate from latency?
Risk of reactivation increases with age

Onset of shingles most common in immunocompromised pts
How does Cytomegalovirus (CMV) spread?
Neonate: Transplacental

Baby: Breast milk, saliva

Adult: Sex, transfusion, transplant
What is the most common cause of congenital infection?
Cytomegalovirus (CMV)
Where does Cytomegalovirus (CMV) remain latent?
Immune cells including lymphocytes and macrophages
What causes Mono?
4/5th of cases EBV

1/5th of cases CMV
What is the leading causes of death in HIV infected patients?
Cytomegalovirus (CMV)

Can cause neuropathy
What are the clinical manifestations of EBV?
Mono

Burkitt's Lymphoma

Nasopharyngeal carcinoma
What cell does EBV infect?
Infects B cells

Causes polyclonal hyperproliferation
What is the cause of Burkitt's Lymphoma?
EBV
How is EBV diagnosed?
Elevated mononuclear wbc count

Measure heterophile AB agglutination

Hairy Leukoplakia in HIV infected pts
What is the cause of Mono symptoms?
Caused by the aggressive T-cell response to the EBV infection and hyperproliferation of B-cells
Where does EBV remain latent?
In the throat and blood for life
What is the cause of Hairy Leukoplakia in HIV patients?
Re-emergence of EBV
What is the clinical manifestation of HHV-8
Kaposi Sarcoma Associated Herpesvirus

See in people with AIDS
What causes HHV-8 virulence?
It inactivates pRb (cellular anti-tumor gene)

Can lead to Kaposi Sarcoma
Pol Gene
Gene in HIV responsible for viral enzymes

Reverse Transcriptase, integrase, protease
gp120
Envelope glycoprotein

Responsible for binding to receptor/co-receptor

Causes bystander killing of uninfected cells by causing them to go through apoptosis
gp41
Envelope glycoprotein gene of HIV

Transmembrane protein that is responsible for fusion to cell membrane
Vif
HIV gene

Overcomes cellular intrinsic immunity of APOBEC3B
Gag
HIV gene

Responsible for structural proteins like Capsid
What does HIV infect?
Predominately CD4 T-cells (T-helper cells)

But can also infect Macrophages and DC
Where does most of the migration and replication of HIV occur?
Occurs in Gut Associated Lymphoid Tissue (GALT)
Where are HIV cells latent?
Latent in Resting Memory CD4- T-cells

Latency not by choice
When can you define full-blown AIDS?
<200 CD4 T-cells
or
<15% of total lymphocytes
and/or
AIDS defining illness
What is the primary screen for HIV?
ELISA assay

Tests for anti-HIV antibodies

Some false positives
What is the confirmatory test for HIV
After ELISA assay

do Western Blot
What are some Oral AIDS defining illnesses?
Candidiasis

Hairy Leukoplakia (EBV infection)

Kaposi Sarcoma (HHV-8 infection)
Reverse Transcriptase Inhibitor
Prevents RNA from being converted to DNA

Inhibits Reverse Transcriptase of HIV
Protease Inhibitor
Prevents cleavage of Gag and Pol during budding of HIV virus

Prevents maturation of the viron therefore no longer infections
Fusion Inhibitor
Prevents the fusion of HIV virion to cell membrane
Integrase inhibitor
Interferes with HIV virus to integrate its DNA molecule into chromosome
What antiviral was introduced that dramatically dropped deaths of people with HIV?
Protease inhibitors

It prevented the cleavage of Gag and Pol enzymes preventing the maturation of the HIV virion

Immature virion is not infectious
Reverse Transcriptase
RNA-dependent DNA polymerase

No proofreading activity

Error rate is great (10^-4 as compared to 10^-11 of cellular DNA polymerase)
Bystander killing of uninfected cells by HIV
Env glycoprotein gp120 causes apoptosis of cells that are not infected by virus

Reason for immunodeficiency since not many T-cells are killed
Long term non-progressors
LTNP

HIV exposed and uninfected individuals

They are associate with a particular MHC allele (Class I B57, B27) that allows them to sustain CD4 cells and maintain lower viral load.
Why is there Immune Exhaustion in HIV infection?
CD8 T-cells initial reduction of viral load

T-cells constantly replicating causing telomere shortening

Eventually run out of T-cells
CD4 because being killed by CD8 cells
and CD8 because can no longer replicate
Are all RNA tumor viruses retroviruses?
Yes
Are all retroviruses RNA tumor viruses?
No
Types of Human Retroviruses
Some are Tumor causing

HTLV-1 / HTLV-2 - can cause T-cell leukemia

HIV-1 / HIV-2 - does not cause cancer directly

Spumavirus

XMRV
Type of DNA tumor viruses
Herpesvirus (specifically EBV, HHV-8)

Papilloma virus

HBV / HCV

Adenovirus
General classification of Retrovirus
Enveloped

+ssRNA

Has viral RNA-dependent DNA polymerase called reverse transcriptase

Integrates into chromosomal DNA
Are retroviruses enveloped or naked?
Enveloped
What is the genome type for retroviruses
+ssRNA
Provirus
An integrated retroviral DNA genome
What is the function of Long Terminal repeats in retroviruses genome?
5' LTR contains promoter
3' LTR contains poly(A) function

It mediates integration of the viral genome into the chromosomal DNA
Rous Sarcoma Virus
Retroviruses found in birds

Known to transform normal cells and make them grow indefinitely causing cancer
What protein helps mediate fusion of the HIV molecule to the cell?
gp41 Transmembrane glycoprotein

Encoded in ENV segment
What protein helps mediate HIV binding to cell receptors?
gp120 Outer Docking Glycoprotein

Encoded in ENV segment
How can retroviruses cause insertional oncogenesis?
Activation of c-onc by inserting retrovirus near it

Inactivation of tumor suppressor gene by inserting retrovirus in it
General characteristics of Human Papilloma Virus
Naked

dsDNA

Icosahedral capsid

Causes genital warts and cervical cancer

Sexually transmitted

TYpes: 16, 18, 6, 11
How is HPV transmitter?
Sexual contact

Direct contact
HPV infection of cutaneous epithelium
Local infection

Causes warts
HPV infection of mucosal epithelium
Can cause cervical carcinoma
What types of HPV cause 70% of cervical cancer?
HPV 16 and 18
What type sof HPV causes 90% of genital warts
HPV 6 and 11
What HPV types are high risk?
HPV 16, 18, 6, and 11
What is the function of E6 and E7 proteins in HPV
E6 inactivates p53 tumor suppressor gene

E7 inactivates pRb tumor suppressor gene
What HPV type is most commonly associated with Oral Squamous Papilloma?
HPV Type 16
Oral Squamous Papilloma
Caused by HPV Type 16

Replicates in skin stem cells

Released from dying cells when they are shed
Gardasil
Vaccinates against all 4 types (16, 18, 6, 11)

Given before infection

Uses L1 capsid proteins to elicit a antibody response
Cervarix
Vaccinates against HPV 16 and 18

No protection against genital warts HPV 6, 11
General properties of Poliovirus
Belongs to Picornavirus family

Naked

+ssRNA

Icosahedral

Three serotypes (Poliomyelitis, Polio, infantile paralysis)

Transmitted fecal-oral route
What type of genome is poliovirus?
+ssRNA
Is poliovirus enveloped or naked?
Naked
How is poliovirus transmitted?
Fecal-oral route
What cells do poliovirus infect?
Primary site of replication is tonsols/oropharynx/peyer patches

Second infection of motor neurons
Polio Vaccines
Type types

Salk - Inactivated Polio Vaccine
-Uses formalin

Sabin - Live Attenuated Vaccine
Replicated well in gut, but not in nervous system --> but can revert to disease
General properties of Arboviruses
Belongs to family Flavivirus

Enveloped

+ssRNA

Icosahedral

Vector of transmission are arthropods

Infections caused by Yellow fever virus, west nile virus, dengue virus
What type of genome do arboviruses have?
+ssRNA virus
Are arboviruses enveloped or naked?
Enveloped
What types of viruses fall under Arboviruses?
Yellow fever virus

West Nile Virus

Dengue virus
General properties of West Nile Viruses
Falls under Arboviruses

Belongs to family Flavivirus

Enveloped

+ssRNA

Icosahedral

Vector of transmission are Ares mosquitos

BIRDS ARE THE MAJOR RESERVOIR
General properties of Dengue Virus
Falls under Arboviruses

Belongs to family Flavivirus

Enveloped

+ssRNA

Icosahedral

Vector of transmission are mosquitos

4 serotypes that USED to be localized

HUMANS ARE THE ONLY RESERVOIR
Antibody Dependent Enhancement of Infectivity
Occurs in Dengue infection

Reinfection of a second serotype results in antibodies from the first infection making the second infection worse