SJSU MICR20 CHAPTER 24

viruses in human infections & disease

- smallest parasites w/ simplest biological structure

- DNA or RNA molecules surrounded by protein coat

- obligate parasites enter cell, instruct its genetic & molecular machinery to produce & release new viruses

- all DNA viruses are double-stranded except parvovirus

- all RNA viruses are single stranded except for reoviruses

medical considerations in viral disease

- viruses limited to particular host or cell type

- most DNA virus are budded off the nucleus

- most RNA virus multiply in & are released from cytplasm

- viral infections range from asymptomatic to mild to life-threatening

- many virus strictly human in origin, others are zoonoses transmitted by vectors

course of viral disease

- invasion at portal of entry & primary infection

- some viruses replicate locally

- others enter circulation & infect other tissue

common manifestations

- rashes

- fever

- muscle aches

- respiratory involvement

- swollen lymph nodes

body defenses

combined action of interferon, antibodies, and cytotoxic T cells

viral infections

- many viral infections have rapid course; lytic cycle

- some establish long-term persistent infections

2 types of persistent infections

- chronic infections

- latent infections

chronic infections

- virus detectable in tissue samples

- multiplying at a slow rate

- symptoms mild or absent

latent infections

- after a lytic cycle, virus enters dormant phase

- generally not detectable

- can reactivate & result in recurrent infections

animal virus

- categorized according to nucleic acid (DNA/RNA), capsid, & presence or absence of envelope

DNA viruses causing human disease

- enveloped DNA virus

- nonenveloped DNA virus

- nonenveloped ssDNA virus

poxvirus

- enveloped

- produce eruptive skin pustules that leave scars

- largest & most complex animal virus

- have largest genome of all viruses

- dsDNA

- multiply in cytoplasm of epidermal cells & subcutaneous connective tissues

smallpox

- first disease to be eliminated by vaccination

- exposure through inhalation or skin contact

- fever, malaise, prostration, rash

- variola major & variola minor

variola major

- highly virulent

- cause toxemia, shock, & intravascular coagulation

variola minor

less virulent

smallpox vaccination

- uses single drop of vaccinia virus punctured into skin w/ double-pronged needle

- routine vaccination ended in US in 1972

- vaccine reintroduced in 2002 for military & medical personnel

herpesviruses

- enveloped DNA

- show latency & cause recurrent infection

- viral DNA forms episome

- clinical complications of latency & recurrent infections become more severe w/ advancing age, cancer, chemotherapy, or other conditions that compromise the immune defenses

- common & serious opportunists among AIDS patients

- humans susceptible to 2 varieties: HSV-1 & HSV-2

episome

- type of genetic element (such as DNA)

- can exist and replicate in the cytoplasm of a cell

- or can integrate into the host chromosome

herpesvirus structure

- large enveloped icosahedral double stranded DNA

- replicated within nucleus

HSV-1

- usually lesions on oropharynx, cold sores, fever blisters

- close contact, usually face

- occurs trigeminal ganglion

- enters 5th cranial nerve

HSV-2

- lesions on genitalia, possibly oral

- sexual or intimate contact

- occurs primarily in sacral ganglia

- enters lumbosacral spinal nerve trunk ganglia

transmission of Herpes Simplex

- by direct exposure to secretions containing the virus

- active lesions are most significant source

- genital herpes can be transmitted in absence of lesions

- HSV multiplies in sensory neurons, moves to ganglia

Herpes Simplex infection

- recurrent infection is triggered by various stimuli - fever, UV radiation, stress, mechanical injury

- newly formed viruses migrate to body surface, producing a local skin or membrane lesion

HSV-1 in children & adults

- Herpes labialis

- herpetic gingivostomatitis especially in young children

Herpetic keratitis

Herpes labialis

- fever blisters or cold sores

- most common recurrent HSV-1 infection

Herpetic gingiviostomatitis

- especially in young children

- inflammation of oral mucosa (gums, tongue, soft palate, & lips)

Herpetic keratitis

- ocular herpes

- inflammation of eye

- latent virus travels into ophthalmic rather than mandibular branch of trigeminal nerve

- gritty feeling in eye, conjunctivitis, sharp pain, & sensitivity to light

Type 2 Herpes infections

- genital herpes

- recurrent bouts usually less severe, triggered by menstruation, stress, & concurrent bacterial infections

genital herpes

- herpes genitalia

- starts with malaise, anorexia, fever, & bilaterial swelling & tenderness in groin

- clusters of sensitive vesicles on genitalia, perineum, & butt

- urethritis, painful urination, cervicitis, itching

- vesicles ulcerate

Herpes of newborn

- HSV-1 & HSV-2 infections potentially fatal in neonate & fetus

- infant contaminated by mother before or during birth; hand transmission by mother to infant

- infection of mouth, skin, eyes, CNS

- preventative screening of pregnant women; delivery of C-section if outbreak at time of birth

diagnosis of Herpes Simplex

- vesicles & exudate are typical diagnostic symptoms

- scrapings from base of lesions showing giant cells

- culture & specific tests for diagnosing severe or disseminate HSV; direct fluorescent antibody tests

treatment of HSV

- acyclovir: inhibit viral DNA synthesis

- famciclovir: inhibit viral DNA synthesis

- valacyclovir: inhibit viral DNA synthesis

Varicella-Zoster Virus

- humans are only natural host

- transmitted by respiratory droplets & contact

- primary infection: varicella (chickenpox)

- reactivation of virus: Herpes zoster (shingles)

chickenpox

- primary infection of varicella-zoster virus

- vesicles

- virus enters neurons & remains latent

Herpes zoster

- reactivation after chickenpox

- dermatomes

- more common in older patients

diagnosis of VZV infection

- cutaneous manifestations of varicella & shingles are sufficiently characteristic for ready clinical recognition

- shingles can be confirmed form multinucleate giant cells in stained smears prepared from vesicle scrapings

- unequivocal shingles identification w/ fluorescent antibody detection of viral antigen in skin lesions, DNA typings, or culture

viral agents of Hepatitis

- DNA virus: Hepadnaviruses (major group) & Hepatitis B Virus

- RNA viruses: Hep. A, Hep. C, Hep. E, & Hep. D

Hepatitis B Virus (HBV)

- produces hepatitis in humans

- multiplies exclusively in liver, which continuously seeds blood w/ viruses (chronic)

- 107 virions/mL blood

- blood products can transmit infection; sexually transmitted

- high incidence among homosexuals & drug addicts

- increase risk of liver cancer (hepatocellular carcinoma)

Hepatitis A virus (HAV)

- from contaminated food

- least virulent

Hepatitis C virus (HCV)

- from fecally contaminated food

- newly identified

- causes disease similar to HAV

Hepatitis D virus (HDV)

- defective RNA virus

- only infects cells already infected w/ HBV

pathogenesis of Hep. B virus

- virus enters break in skin or mucous membrane or by injection into bloodstream

- reaches liver cells, multiplies, & releases viruses into blood

- avg. 7 week incubation

- most exhibit few overt symptoms & eventually develop HBV immunity

- some experience malaise, fever, chills, anorexia, abdominal discomfort, & diarrhea

- fever, jaundice, rash, arthritis (severe case)

- small # of patients develop chronic liver disease - necrosis & cirrhosis

Adenovirus

- nonenveloped, dsDNA

- 30 types associated w/ human disease (oncogenic only in animals)

- infect lymphoid tissue, respiratory, & intestinal epithelia

- spread by respiratory & ocular secretions

- cause cold, pharyngitis, conjunctivitis, keratoconjunctivitis, acute hemorrhagic cystitis

- severe cases treat w/ interferon

- inactivated polyvalent vaccine

Parvovirus

- nonenveloped, ssDNA

- small diameter & genome size

- cause distemper in cats, enteric disease in dogs, fatal cardiac infection in puppies

- few cause infection in humans

human parvovirus

- B19 cause of erythema infectiosum (5th disease); rash of childhood

- children may have fever & rash on cheeks

- severe fatal anemia can result if pregnant woman transmit virus to fetus

- adeno-associated virus (AAV) is defective virus; cannot replicated in host cell without adenovirus

Epstein-Barr virus

- member of Herpesviridae family

- one of most common viruses in humans

- primarily transmit through saliva (kissing disease); can transmit through other bodily fluids

- cause infectious mononucleosis

- latent infection in B lymphocytes; virus can reactivate

- treatment: only relievement

- no vaccine

Cytomegalovirus

- member of Herpesviridae

- common virus - can infect all ages

- primarily transmit through bodily fluids & sexual contact

- can transmit through mother to child during pregnancy, childbirth, or breastfeeding

- flu-like symptoms

- can remain dormant, reactivate later

- congenital infections - lead to hearing loss, developmental delays

Herpetic whitlows

- painful infection caused by HSV that affects fingers or thumbs

- usually transmitted through direct contract w/ infected area, such as oral or genital lesions

symptoms of Herpetic whitlows

- initial symptoms: localized pain, itching, or burning at site of infection

- swelling & redness

- painful blisters/vesicles

Syncytium

- multinucleated cell that forms from fusion of multiple individual cells

- caused by HIV, RSV & herpesviruses

- can facilitate spread of virus b/w cells while evading immune response

Giant cells

- specialized, large cells that can form from fusion of macrophages or other immune cells

- can be multinucleated & seen in inflammatory responses

- types of giant cells: Langhans Giant Cells & Foreign Body Giant Cells

- indicative of chronic inflammation

- play role in body's immune response to persistent infections or foreign substances

Langhans Giant Cell

- characterized by horseshoe arrangement of nuclei

- typically associated w/ granulomatous inflammation

- ex. tuberculosis

Foreign Body Giant Cells

formed in response to foreign materials

infectious mononucleosis

- primarily caused by Epstein-Barr virus

- fatigue, fever, sore throat, swollen lymph nodes, enlarged spleen

Burkitt's Lymphoma

- type of aggressive non-Hodgkin lymphoma

- characterized by rapid proliferation of B lymphocytes

- associated w/ Epstein-Barr Virus

- most common in children

- rapidly growing tumors in abdomen, jaw, or lymph nodes

Human papillomavirus (HPV)

- nonenveloped

- 55nm

- common in human carriers

- virulence factor: ability to persist in epithelial cells of genitalia

-can insert in genome & cause oncogenesis

- common warts, plantar warts, genital warts

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