s l 2013 DNA VIRUSES 1 Virus Characteristics Epidemiology Pathogenesis and Virulence Diseases Lab Diagnosis Treatment

Herpes Simplex Virus

(Herpesviridae)

Icosahedral Enveloped Double stranded

linear 2 types: HSV-1 and

-2 Lifelong infection

Spread: direct contact (orally or sexually)

Location: neurons and epithelia (latency)

Risk Factors: 1. Contaminated fingers 2. Birth canal transmission 3. Kissing

At Risk: 1. Children and sexually active people 2. Health care workers 3. Immune compromised or neonates

Pathogenesis 1. Skin penetration and replication 2. Enters cutaneous sensory neurons

and ascends to ganglia to establish latency

3. Virus can be reactivated and can travel via neurons recurrent infection

Virulence 1. Direct cytopathologic effects 2. Syncytia formation: cell-cell spread,

avoids antibodies 3. Latency in neurons!! 4. CMI is required for resolution HSV-1: trigeminal ganglia to naso-

oral epithelia HSV-2: sacral ganglia to urogenital

epithelia

1. Herpes gingivostomatitis: initial primary infection

2. Herpes labialis or Cold sores: painful shallow ulcers on lips accompanied by fever, malaise and myalgia; usually heal without scarring in 8 to 10 days

3. Herpetic whitlow: thumb lesion 4. Keratoconjunctivitis: corneal scarring and blindness (2nd most common cause)

5. Encephalitis: if virus spreads to CNS Risk for Reactivation: 1. Stress (UV, emotional) 2. Immune suppression 3. Spicy/ acidic food 4. Menstruation 5. Fever

Visual diagnosis

Tzanck smear: multi-nuc giant cells and cowdry A inclusion bodies

Cell culture Serology: type specific Ab (HSV-1 vs -2)

Acyclovir Foscarnet

Varicella Zoster Virus

(Herpesviridae)

Icosahedral Enveloped Double stranded

linear Lifelong infection Primary and

Recurring disease

Spread: respiratory droplets

Location: neurons and epithelia (latency)

At Risk: 1. Children (5-9yo) 2. Teens and adults 3. Immune compromised or neonates

Pathogenesis 1. Initial respiratory infection 2. Viremia: spread of virus to nerves and

skin 3. Establish latency in DRG or CN ganglia 4. Reinfection spreads along dermatome 5. Vesicle progression: macule papule vesicles pustules crusts

Virulence 1. Viremia 2. Escape Ab clearance 3. Latency!

Varicella (Chicken Pox) 1. mild asymptomatic disease - fever, maculopapular rash 2. Within hours, each lesion turns into thin-walled vesicle (glue drop on rose petal) 3. Vesicle (hallmark!): Rash spreads from trunk; reaches scalp 4. Itchy lesions scratching invites secondary bacterial superinfection

Herpes Zoster (Shingles) 1. Severe pain precipitates lesions 2. Spread along dermatome 3. Post-herpetic neuralgia: chronic pain after infection

Same as HSV VarizIg neutralizing Ab

Live attenuated vaccine: children

Cytomegalovirus (Herpesviridae)

Icosahedral Enveloped Double stranded

linear Recurrent infection Congenital

infection

Spread: saliva, body fluids

Location: monocytes and macrophages (latency)

Risk Factors: 1. Immunocomp 2. Giving birth 3. Sexual intercourse 4. Blood transfusion

Pathogenesis 1. Initial infection through blood (monocytes and macrophages) 2. Establish latency in infected macrophages 3. Primary infection is subclinical (asymptomatic) Virulence 1. Viremia 2. Latency

1. Infectious mononucleosis: common infection of adults; fever, muscle pain, lymphadenopathy (similar to EBV IM)

2. Cytomegalic Inclusion disease: infection during pregnancy; small baby, microcephaly, jaundice, hearing loss, mental retardation, cataracts

3. Multisite symptomatic disease: often in immune compromised; pneumonia, meninigitis, hepatitis, encephalitis, failed renal transplant

Owls eye inclusion body

Serology: Ag detection

PCR Absence of atypical lymphocytes and heterophile Ab

Ganciclovir Foscarnet Screening

reduces intrauterine transmission

s l 2013 DNA VIRUSES 2 At Risk:

1. Neonates 2. Sexually active people 3. Immune compromised 4. Burn victims

Epstein-Barr Virus

(Herpesviridae)

Icosahedral Enveloped Double stranded

linear Linked to

malignancy

Spread: saliva, body fluids

Location: memory B cells (latency)

At Risk: 1. Teenagers 2. Children 3. Immune compromised

Pathogenesis 1. Initial replication in oropharynx 2. Infect B cells via C3b receptor 3. Establishes latency 4. Virus replicates when B cells

replicate 5. T cells try to eradicate B cells Virulence 1. Latency 2. Immortalization of B cells 3. Polyclonal B-cell proliferation 4. T cell activation leads to disease

manifestation (IM)

1. Infectious mononucleosis: fever, myalgia, splenomegaly and lymphadenopathy (same as CMV)

2. Burkitt Lymphoma: translocation of c-myc gene on chrom 8 to Ig heavy chain gene on chrom 14; malignancy of jaw

3. Hairy Oral Leukoplakia: EBV infection on epithelium lesions on mouth; full blown AIDS

4. EBV-associated nasopharyngeal carcinoma

5. EBV infection for immunocompromised: can sufficiently cause B cell lymphomas

CBC: lymphocytosis

Atypical lymphocytes

Heterophile Ab

Paul-Bunnell Test

EBV specific Ag 1. EA first Ab 2. VCA IgM then IgG 3. EBNA marker of infection; last to develop

No vaccine Acyclovir?

Parvovirus (Parvoviridae)

Icosahedral Non-enveloped Single stranded

linear Smallest virus

Spread: respiratory Location: erythroid

progenitor cells Risk Factors:

1. Sickle cell disease 2. Pregnancy (first trimester highest risk)

At Risk: 1. Elementary school students 2. Parents of children with B19

1. Viremia: high titer virus infection lasting 1 week after infection

2. Infection of rapidly dividing cells primarily erythroblasts

Two phases: 1. Initial Viremia 2. Immune Response: immune complex

deposition

1. Flu-like symptoms: Initial consequence of early phase viremia

2. Erythema infectiousum or 5th disease: slapped-cheek rash on the face due to immune complex deposition

3. Aplastic crisis in individuals with chronic anemia (sickle cell): fever, chills, malaise, itching, rash

4. Polyarthritis: symptoms in many joints

Clinical presentation

ELISA IgM PCR

No antiviral agent or vaccine

IVIG for B19 virus in immunocomp

Adenovirus (Adenoviridae)

Icosahedral Non-enveloped Double stranded

linear 50 serotypes Used as a vector

for gene therapy

Spread: respiratory and feco-oral

Location: intestine, eyes, respiratory tract

Risk Factors: 1. Contaminated hands 2. Ophthalmologic instruments 3. Swimming water

At Risk: 1. Infants

1. Enters cell via receptor-mediated endocytosis

2. Inactivates p53 and Rb 3. Shuts off DNA, RNA and protein

synthesis 4. Release of infected virus comes from

disintegration of dying cell

1. Acute febrile pharyngitis: strep throat-like in children and infants

2. Pharyngoconjunctival fever: pharyngitis and conjunctivitis

3. Acute respiratory disease: military recruits

4. Pertussis-like syndrome: infants and young children; use the cough-plate method

**All can progress to pneumonia 5. Meningoencephalitis 6. Keratoconjunctivitis: inflamed pebbled conjunctiva; transmission by

ELISA PCR culture

Live vaccine for serotypes 4 & 7 given to military personnel

Serology neutralization

s l 2013 DNA VIRUSES 3 2. Military recruits low resistance to virus & exposure to new strains

sharing of towels, unsterilized ocular instruments

7. Gastroenteritis: infantile diarrhea with vomiting (5-15% of viral diarrhea in children); serotypes 40-42

8. Acute hemorrhagic UTI: bone marrow recipients

9. Hepatitis: liver transplant recipients Human

Papilloma Virus (HPV)

(Papovaviridae)

Icosahedral Non-enveloped Double stranded

circular High risk for

cervical carcinoma (HPV 16 and 18)

Spread: sexual contact, fomites, transplacental

Location: differentiated epithelial cells

Risk Factors: 1. Pregnancy 2. Unprotected sex

1. Infects epithelial cells and its differentiation state (cutaneous epithelia or mucosal epithelia) tropism, permissivity and immortalizing infection

2. Access to epithelial cells is most likely due to surface lesions (abrasions)

3. Wart formation: papillomavirus early proteins facilitate migration of virus from basal layer to surface

4. Carcinoma: binding between early proteins and p53 and Rb increases risk of malignancy, require integration of viral genome in host chromosome

1. Skin warts (types 1-4): keratinized surface, benign and self-limiting, regresses with time; mainly on hands, fingers and feet; could lead to squamous cell carcinoma

2. Laryngeal papilloma (types 13 & 32): benign; due to infection of oral and nasopharyngeal mucosa

3. Anogenital warts/Condyloma accuminata (mostly type 6 & 11): benign growth on squamous epithelia

4. Cervical cancer (type 16, 18): carcinoma in situ, integrate into host chromosome; E6/E7: inactivate p53 and Rb; E5: enhances EGF

Visual inspection

PCR: determine whether HPV is high risk

Gardasil: vaccine against HPV 6, 11, 16 and 18

Surgical removal or destruction of warts

Human Polyoma Virus

(Papovaviridae)

Icosahedral Non-enveloped Double stranded

circular Three human

subtypes: JC, BK, & MC

Spread: respiratory and urine

Location: CNS, urinary tract

Risk Factors: 1. Immune compromised

At Risk: 1. Children

1. Spread from URT to kidneys (inactive state)

2. Reactivation: viral replication, cell death and viral release

JC virus:

1. Viremia: spread to CNS 2. Reactivated in oligodendrocytes 3. Demylination

BK virus: UTI in immunocompromised

1. Progressive multifocal leukoencephalopathy (JC): mental and sensory abnormalities, paralysis and impared speech

2. UTI (BK)

Most people have Ab to viruses

DNA hybridization

No preventive measures

Variola Virus (Poxviridae)

Complex Enveloped Double stranded

linear Eradicated from

Earth

Spread: none Risk Factors:

1. Mutations in animal poxviruses

At Risk: 1. Unvaccinated

1. Replication in cytoplasm: rapid, shuts off cell synthesis and leads to cell death and viral release

Secondary infections None Smallpox vaccine

**Post-vaccinal

encephalitis can occur

Other Medically Important DNA Viruses HHV 6 Roseola HHV 8 Kaposis Sarcoma