Mhr Topic 26: Enveloped Dna Viruses

Front 1

Herpesviruses (Size, envelope, complexity)

Back 1

Large, enveloped, very complex with many virus specific enzymes (drug targets) and less dependence on host function.

Front 2

Herpesviruses (genetic material, transmission, replication location, integration)

Back 2

Double stranded DNA
Transmission via close contact
Replication is in the nucleus
viral genome DOES NOT INTEGRATE

Front 3

What is the defining pathogenetic feature herpesviruses?

Back 3

Latency

Front 4

Herpesviruses subclass alpha (Replication speed, cellular effects, outcome, site of letency, examples)

Back 4

1) Fast replication
2) Shuts down cell
3) Cytolytic
4) Latent in nerve ganglia
5) Herpes simplex 1, 2, and varicella zoster virus

Front 5

Herpesviruses subclass beta (Replication speed, cellular effects, outcome, site of letency, examples)

Back 5

1) Slow Replication
2) No cellular effect
3) Cytomegalic lytic
4) Latent in lymph nodes and glands
5) Human cytomegalovirus, human herpesvirus 6 and 7.

Front 6

Herpesviruses subclass gama (Replication speed, cellular effects, outcome, site of letency, examples)

Back 6

1) Slow Replication
2) Activates Cell
3) Proliferative
4) Latent in B cells and monocytes
5) Epstein-Barr virus, human herpesvirus 8(Kaposis sarcoma herpesvirus)

Front 7

Which herpesviruses are sexually transmitted?

Back 7

Herpes simplex 1
Herpes simple 2
Human cytomegalovirus
Human herpesvirus 8 (Kaposis sarcoma herpesvirus)

Front 8

Thymidine kinase

Back 8

Enzyme involved in nucleic acid metabolism encoded by herpesviruses. Especially important for alpha herpesviruses b/c they must replicate in non-dividing cells (neurons).

Front 9

General steps/points of herpesvirus replication

Back 9

Transcription and Viral DNA replication occur in the nucleus
Translation Occurs in the cytoplasm
Viron assembly occurs in the nucleus
Productive infection is lytic (host cell dies)

Front 10

Uncoating

Back 10

Occurs at the plasma membrane. Capsid and tegument are transported to the nuclear pore via the cytoskeleton. Viral DNA and parts of the teguments are then released into the nucleus.

Front 11

What is the protein which causes herpesvirus genome replication?

Back 11

Viral DNA polymerase (is a target of drugs)

Front 12

What type of herpesviruses do not establish latent infections?

Back 12

NONE! all herpesviruses establish latent infections.

Front 13

What is the protein which causes herpesvirus initial transcription?

Back 13

The hosts RNA Polymerase II

Front 14

Primary Infection

Back 14

First exposure to HSV

Front 15

Initial Infection

Back 15

Exposure to HSV 1or 2 after primary infection with the other type.

Front 16

Recurrent Infection

Back 16

Virus shedding (possibly with disease) after reactivation from latency.

Front 17

Neurotropic

Back 17

Infecting primarily epithelial cells, fibroblasts, and ultimately sensory neurons. HSV 1 and 2 are neurotropic.

Front 18

HSV contraction

Back 18

Contracted through contact with saliva or sexual activities

Front 19

Herpes labialis, keratitis, genitalis, whitlow, and gladitorum

Back 19

Labialis = mouth or throat
keratitis = eye
genitalis = genitals or anus
whitlow = healthcare workers get finger infection through broken skin
gladitorium = wrestlers get skin infections

Front 20

HSV Infection and life cycle

Back 20

1) Mucosal Infection - Virus and fluid filled vesicles appear, lesions form as cells die. Virus enters axons of sensory nerves near site of infection.
2) Latency - Viral genome is maintained in sensory neurons without virion production. Neurons dont express MHC so immune system is avoided. HSV 1 goes to TG ganglion from oropharynx or eyes, HSV 2 goes to sacral DSG from genitals or anus. Genome is circular episome; not integrated.
3) Reactivation - Stimuli which effects neuron or immune system triggers reactivation (stress, tissue damage, uv light, steroids). Reactivated viruses go back to epithelial cells via neuron, establish a new lesion (ex, cold sore). Sometimes this can be minor with no vesicle formation but still contagious. Immune sys. can control mucosal infection but not neural. Latent period is then established in new neuron.

Front 21

What type of immunity is most important in control of HSV?

Back 21

Cell mediated.

Front 22

Who gets systemic infections of HSV?

Back 22

Immunocompromosed patients and in babies with low levels of maternal antibodies and immature immune systems.

Front 23

How is frequency of reactivation related to age?

Back 23

Decreases with age.

Front 24

Oropharyngeal HSV Infection

Back 24

Usually HSV1. Transmission via kissing or hands to mouth. Most of world is infected by adulthood.

Front 25

Oropharyngeal HSV primary vs recurrent infection

Back 25

Primary - Often asymptomatic. Can have local rash, tender gums, pharyngitis, tonsillitis. Pain, fever, malaise, submandibular lymphadenopathy. Incubation = 2-12 days. Duration = 2-3 weeks (virus shedding is only half this).
Recurrent - Half exposed have recurrent. Symptoms are labialis (cold sore) as vesicles near skin/lip border, preceded by pain, itching, burning. Incubation = 24-48 hrs after these prodromal symptoms. Duration = 8-10 days.

Front 26

Genital HSV Infection

Back 26

Usually HSV 2. Is an STD. 17% of US adults have.

Front 27

Genital HSV primary vs recurrent infection

Back 27

Primary - Often asymptomatic. Symptoms are local vesicular rash, local ulcers, fever, malaise, dysuria, lymphadenopathy. Incubation = 5-7 days. Duration = 2 weeks.
Recurrent - Typically milder than primary infections. Same general symptoms as Primary. Incubation = 24-48 hours post prodrome. Duration = 4-7 days. Only 20% show symptoms when shedding, 80% have asymptmatic shedding. + correlation with HIV

Front 28

HSV Keratoconjunctivitis

Back 28

Transmission via hand to eye. Symptoms are dendritic lesion, corneal ulcers, vesicles, photophobia. Immunopathologic response to recurrence leads to corneal scarring and blindness. Most frequent cause of corneal blindness due to infection.

Front 29

HSV Encephalitis

Back 29

Can be caused by primary or recurrent infection. Symptoms include fever, headache, seizures, and altered mental behavior. Blood is clean but CSF has ^WBCs. Most common viral cause of encephalitis and spontaneous encephalitis.

Front 30

Neonatal Herpes

Back 30

Infection occurs during peripartum period or postnatally. Transmission highest during primary infection. Higher in developing countries. C sections and screening used to reduce risk.
Disease can be 1) skin and mouth, 2) CNS (accompanied by seizures) 3) Widely disseminated (50% fatal). Can have ulcerated lesions, fever, and seizures.

Front 31

HSV Diagnosis

Back 31

Appearance and distribution of vesicles is main. DNA PCR and immunoflouresence is fastest.

Front 32

Varicella-Zoster Virus Latency Location

Back 32

Sensory Neurons at all levels.

Front 33

Varicella-Zoster Virus Infection and Transmission

Back 33

Transmitted via aerosols and respiratory droplets. Primary replication occurs in oropharynx and upper respiratory tract. Spreads to other sites. Infectivity is greatest 48 hours before rash and 3-4 days post rash.

Front 34

Varicella-Zoster Virus Primary vs reactivation infection

Back 34

Primary - Varicella (chicken pox). Symptoms are fever, anorexia, malaise precede disseminated papulovesicular rash. Starts trunk goes to extremeties. Incubation = 14-21 days, Duration = 2-6 days.
Reactivation - Herpes Zoster (Shingles). 15% of people get usually >50. Only occurs once. Symptoms are pain, burning itching followed by a vesicular rash which only covers a single dermatome. Can also get post-herptic neuralgia. Duration = vesicles form for 3-7 days, heal in 14.

Front 35

Varicella-Zoster Virus Diagnosis

Back 35

Rash is usually diagnostic. Definitive ID is via cell culture.

Front 36

ie1/2

Back 36

Very strong immediate early promoter-enhancer of human cytomegalovirus. Often used in molecular biology.

Front 37

Human Cytomegalovirus Transmission

Back 37

Person to person contact. Vaginal secretions, semen, breast milk, saliva, sputum, urine, feces, blood all can transmit virus. Can also be transferred by transplants and via birth.

Front 38

Human Cytomegalovirus Congenital infection/disease

Back 38

Mothers undergoing primary infection during pregnancy are usually asymptomatic but are more likely to transmit infection. Most severe infections result from first trimester infection.
Causes cytomegalic inclusion disease (CID) leading to congenital abnormalities (most common cause of congenital abnormalities). Get petichial rash, purpura, hepatosplegnomegaly, jaundice, microencephaly, hearing loss, and mental retardation.

Front 39

Human Cytomegalovirus Adult infection/disease

Back 39

Can cause mononucleosis during primary infection. Can be distinguished from EBV-induced via absence of heterophile antibodies.

Front 40

Human Cytomegalovirus Disseminated infection

Back 40

Occurs in immunocompromised. Often people who were infected reactivate upon immunosupression. Post transplant HCMV infections are a big deal in kidney and bone marrow transplants (as well as liver and heart). Symptoms are pheumonitis, rertinitis, and hepatitis as well as GI and CNS infections.

Front 41

Human Cytomegalovirus Diagnosis

Back 41

Rapid diagnosis can be done via PCR or immunochemistry. Urine is best indicator of disease. Can see giant cells with "owl eyes." Can also culture. Prenatal testing done by looking for Ab in serum

Front 42

Human Herpesvirus 6,7 Transmission/Infection/latency

Back 42

Transmission is via saliva. Nearly all children infected by age 3.
Replicates in many cell types; 6A prefers skin and brain, 6b prefers mononuclear cells and salivary glands.
Latency is in mononuclear cells

Front 43

Human herpesvirus 6,7 Primary disease vs reactivation

Back 43

Primary - 6B and 7 can cause exanthum subitum (roseola infantum) in infants which is high fever with a macular skin rash on neck and torso. Also a common cause of infantile seizures without rash.
Reactivation - Only occurs in immunocompromised and AIDS patients. Get fever, rash, encephalopothy, pneumonitis and hepatitis.

Front 44

Human Herpesvirus diagnosis

Back 44

PCR or serologic ID

Front 45

Human Herpesvirus 8 Transmission

Back 45

In US strictly an STD. In other countries can observe vertical transmission.

Front 46

Human herpesvirus 8 Primary vs reactivation disease

Back 46

Primary - Replicates in mononuclear cells. No known symptoms.
Reactivation - Causes Karposi's sarcoma. Disease only associated with latent infection. During latency, virus encoded and host cytokines drive endothelial and fibroblast prolif leading to vascular lesions with spindle cell aggregates. Causes body cavity lymphoma in AIDS patients (a defining illness). Can also cause Castleman's disease (a polyclonal neoplasia).

Front 47

Epstein-Barr Virus Primary Infection and disese

Back 47

Causes infections monomucleosis. Virus causes activation and proliferation of B cells and T cells. Symptoms are due to cytokine secretion and profound lymphocyte expansion. Cause fever, pharyngitis, fatigue and lymphadeno-pathy. Duration = 2-4 weeks and occurs at same time as abnormal lymphocytes. Shedding from oropharynx occurs in 1/4th during recovery.

Front 48

Epstein-Barr Virus Diagnosis

Back 48

Via Mono-Spot test for heterophile antibodies which detects EBV enduced IgM antibodies. Can do blood smears and look for Downey Cells (atypical T lymphocytes).

Front 49

EBV Cancers

Back 49

1) Burkitt's lymphoma
2) Nasopharyngeal carcenoma
3) Oral hairy leukoplasia
4) Post-transplant lymphoproliferative disease
5) Hodgkins lymphoma
6) Non-hodgkins lymphoma

Front 50

Burkitts lymphoma

Back 50

Caused by EBV. Rapidly evolving mononuclear tumor which starts in jaw and goes to kidney liver lymph or GI. Found in equatorial africa.

Front 51

Nasopharyngeal carcenoma

Back 51

Caused by EBV. epithelial cell malignancy. Found in southern chinese and SE asian. Risk factor is eating salted fish.

Front 52

Oral hairy Leukoplasia

Back 52

Caused by EBV. Wart like lesions on tongue. Hit squamous epithelium. Seen in aids patients.

Front 53

Post transplant lymphoproliferative disease

Back 53

Caused by EBV. Malignant lymphoma in immunosupressed.

Front 54

Hodgkin's Lymphoma

Back 54

Caused by EBV 50% of time. Viral DNA found in Reed-sternburg B cells.

Front 55

Non-Hodgkin's Lymphoma

Back 55

Caused by EBV. Polyclonal B cell lymphoma. Defining illness for AIDS.

Front 56

Main differences between herpesviruses and poxviruses

Back 56

Pox viruses replicate in the cytoplasm, provide all replicative enzymes, and do not establish latency.

Front 57

Pox Genome

Back 57

Large, double stranded DNA.

Front 58

Viriola

Back 58

Human pathogen which caused smallpox

Front 59

Molluscum contagiosum

Back 59

Human pox pathogen which can cause benign warts and can be an STD

Front 60

What drugs are HBV treated with?

Back 60

Nucleoside analogs and INF

Front 61

What drugs are HBC treated with

Back 61

INF

Front 62

What does acyclovir target?

Back 62

Thymidine kinase

Front 63

HSV Treatment

Back 63

Acyclovir

Front 64

Reyes syndrome

Back 64

Disseminated primary chicken pox infection

Front 65

Human cytomegallovirus treatment

Back 65

Has no thimidine kinase therefore no acyclovir