DNA & RNA Viruses Flashcards
What are viruses made of?
1) Viruses are particles composed of an internal core containing either DNA or RNA (not both) covered by a protective protein coat
2) Some have outer lipomembrane protein (envelope) external to coat
3) Do not have nucleus, cytoplasm, mitochondria or ribosomes
How do viruses reproduce?
Within cells (they are obligate intracellular parasites) because they cannot generate energy or synthesis proteins
The difference between a virus replicating and a prokaryotic or eukaryotic cell replicating
Viruses do not undergo binary fission or mitosis. One virus can replicate to produce hundreds of progeny viruses, whereas one cell divides to produce only two daughter cells
Comparison of viruses and cells:
1) Type of nucleic acid
2) Proteins
3) Lipoprotein membrane
4) Ribosomes
5) Mitochondria
6) Enzymes
7) Multiplication by binary fission or mitosis
1) Type of nucleic acid: Viruses: DNA or RNA but not both Cells: DNA & RNA 2) Proteins: Viruses: few Cells: many 3) Lipoprotein membrane: Viruses: Envelope present in some viruses Cells: Cell membrane present in all cells 4) Ribosomes: Viruses: Absent Cells: Present 5) Mitochondria: Viruses: Absent Cells: Present in eukaryotic cells 6) Enzymes: Viruses: None or few Cells: many 7) Multiplication by binary fission or mitosis Viruses: No Cells: Yes
The shape of virus particles is determined by the arrangement of?
The repeating subunits that form the protein coat (capsid) of the virus
The viral nucleic acid (genome) is located internally and can be?
Either single or double stranded DNA or single or double stranded RNA
Only viruses have genetic material composed of?
Single or double stranded DNA or single stranded or double stranded RNA. The nucleic acid can either be linear or circular. DNA is always a single molecule; RNA can exist as either a single molecule or in several pieces (for example both influenza virus and Rotavirus have a segmented RNA genome)
The nucleic acid of viruses is surrounded by?
- A capsid (protein coat) made up of subunits called capsomers
- Capsomers consists of one or several proteins
The structure composed of the nucleic acid genome & the capsid proteins is called?
Nucleocapsid
Viral nucleocapsids have 2 forms of symmetry
1) Icosahedral- capsomers arranged in 20 triangles that form a symmetric figure
2) Helical- capsomers arranged in hollow coil that appears rod-shaped. Rigid or flexible.
* All human viruses that have a helical nucleocapsid are enclosed by an outer membrane (envelope)
* Viruses that have a icosahedral nucleocapsid can be enveloped or naked
What is the advantage of building the virus particle from identical protein subunits? It is twofold
1) Reduces need for genetic information
2) Promotes self assembly
Viral proteins serve several important functions
1) Outer capsid proteins protect genetic material & mediate attachment of virus to specific receptors on host cell surface. (This interaction is the major determinant of species & organ specificity)
2) Important antigens- induce neutralizing antibody & activate cytotoxic T cells to kill virus infected cells
3) Also target of antibodies
4) Some are structural others are enzymes
5) Some have DNA or RNA polymerase attached to genome
6) Some contain regulatory proteins in the virion in a structure called the tegument, these proteins include transcription and translation factors that control either viral or cellular processes
How are viral proteins a target for antibodies?
Antibodies bind to these proteins & prevent (neutralize) the virus from entering the cell and replicating
* The outer proteins induce these immune responses following both the natural infection & immunization
Some viruses produce proteins that act as “super-antigens”
Viruses known to produce superantigens include two members of the herpes virus family, Epstein-Barr virus and cytomegalovirus, & the retrovirus mouse mammary tumor virus
The herpesvirus family contains 6 important human pathogens
1) Herpes simplex virus types 1 & 2
2) Varicella-zoster virus
3) Cytomegalovirus
4) Epstein-Barr virus
5) Human herpes virus 8 (cause of Kaposi’s sarcoma)
All herpes viruses are structurally similar
- Each has icosahedral core surrounded by lipoprotein envelope
- Genome linear double stranded DNA
- Virion does not contain a polymerase
- Large (2nd in size to poxviruses)
How do herpes viruses replicate?
- In nucleus
- Form intranuclear inclusions
- Only viruses that obtain envelope by budding from nuclear membrane
- Virions posses a tegument which contains regulatory proteins (transcription/translation factors) which play a role in viral replication
Herpes viruses are noted for their ability to cause latent infections, meaning?
- Acute disease is followed by an asymptomatic period during with the virus remains in a quiescent (latent) state
- When patient exposed to an inciting agent or immunosupression occurs, reactivation of virus replication & disease can occur
Shortly after HSV infects neurons what happens?
A set of latency-associated transcripts are synthesized (these noncoding, regulatory RNAs suppress viral replication)
* process by which latency is terminated & reactivation of viral replication occurs is unclear, but various triggers such as sunlight, fever, & stress are known
CMV established latency by?
Producing microRNAs that inhibit the translation of mRNA’s required for viral replication.
*Genome encodes a protein and an RNA that have the ability inhibit apoptosis in infected cells, this allows infected cell to survive
Three of the herpes viruses cause a vesicular rash
Herpes simplex virus types 1 & 2 and varicella-zoster virus. Both in primary infections and in reactivations. Primary infections are usually more severe than reactivations
Four herpes viruses induce the formation of multinucleate giant cells
Herpes simplex virus types 1 & 2, varicella-zoster virus, & cytomegalovirus
The herpes virus family can be subdivided into three categories based on the type of cell most often infected & the site of latency
1) The alpha herpes viruses, consisting of herpes simplex viruses type 1 & 2, & varicella-zoster virus infect epithelial cells primarily & cause latent infection in neurons
2) The beta herpes viruses, cytomegalovirus & human herpes virus 6, infect & become latent in a variety of tissues
3) The gamma herpes viruses, Epstein-Barr virus & human herpes 8 (kaposi’s sarcoma associated virus) infect & become latent in primarily in lymphoid cells
Certain herpes viruses are suspected of causing cancer
In humans, e.g Epstein-Barr virus is associated with lymphoma and nasopharyngeal carcinoma, & human herpes virus 8 is associated with Kaposi’s sarcoma. Several herpes viruses cause cancer in animals
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are distinguished by two main criteria
Antigenicity and location of lesions.
- Lesions caused by HSV-1 are above the waist
- Lesions caused by HSV-2 are below the waist
Herpes simplex virus 1 (HSV-1) causes?
Acute gingivostomatitis, recurrent herpes labialis (cold sores), keratoconjunctivitis (keratitis), and encephalitis
Herpes simplex virus 2 (HSV-2) causes?
Herpes genitalis (genital herpes), neonatal herpes, & aseptic meningitis
Infection by HSV-1 and HSV-2 is a common cause of?
Erythema multiforme
Important properties of HSV-1 and HSV-2
- Structurally and morphologically indistinguishable
- Can be differentiated by restriction of endonuclease patterns of their genome DNA & by type-specific monocleonal antisera
- Humans natural host of both viruses
The replication cycle of HSV-1 begins when? Same cycle for Varicella-zoster
1) HSV-1 binds first to heparin sulfate on the cell surface and then to a second receptor nectin.
2) Following fusion of the viral envelope w/the cell membrane, the nucleocapsid & the tegumented proteins are released into cytoplasm.
3) Viral nucleocapsid transported to nucleus where it docks to a nuclear pore & the genome DNA enters nucleus along with tegument protein (VP16)
4) Linear DNA becomes circular
5) VP16 interacts w/cellular transcription factors to activate transcription of viral immediate early genes (IE) by host cell RNA polymerase
6) IE mRNA is translated into IE proteins that regulate the synthesis of early proteins (DNA polymerase) that replicates genome & thymidine kinase (these two proteins are important because they are involved in the action of acyclovir (most important drug effective against HSV
Early protein synthesis by HSV can be subdivided into two categories
“Immediate early” and “early”
Immediate early proteins are those whose mRNA synthesis is activated by a protein brought in by the incoming parental vision.
* No new viral protein synthesis is required for the production of five “immediate early” proteins. The “early” proteins do require the synthesis of new viral regulatory proteins to activate the transcription of their mRNAs
For HSV-1 and 2, the viral DNA polymerase replicates the genome DNA, at which time early protein synthesis is shut off and late protein synthesis begins. These late structural proteins are?
Transported to the nucleus, where virion assembly occurs
In latently infected cells, such as HSV-infected neurons, circular HSV DNA resides in the nucleus and is not integrated into cellular DNA. Transcription of HSV DNA is limited to?
A few latency associated transcripts (LATS). These noncoding regulatory RNAs suppress viral replication. Reactivation of viral replication can occur at a later time when the genes encoding LATS are excised.
How is HSV-1 transmitted?
Primarily in saliva, as a result they occur mainly on the face.
However, oral-genital sexual practices can result in infections of the genitals
* Transmission occurs most often when active lesions are present, asymptomatic shedding of both HSV-1 & 2 does occur and plays an important role in transmission
How is HSV-2 transmitted?
By sexual contact, as a result lesions occur in the genital area. However oral-genital sexual practices can result in lesions in the oral cavity (occurs in 10-20% of cases).
* Transmission occurs most often when active lesions are present, asymptomatic shedding of both HSV-1 & 2 does occur and plays an important role in transmission
The number of HSV-2 infections has _________ in recent years, whereas HSV-1 infections have. Roughly ___% of people in the US are infected with HSV-1 and ___% have recurrent herpes labialsis
HSV-2 has increased
HSV-1 has not
80%
40%
Most primary infections by HSV-1 occurs in?
Childhood, as evidenced by the early appearance of antibody. In contrast, antibody to HSV-2 does not appear until the age of sexual activity
Pathogenesis of HSV
- Virus replicates in skin or mucous membrane at initial site of infection, then migrates up neuron by retrograde axonial flow & becomes latent in the sensory ganglion cells. (HSV-1 becomes latent in trigeminal ganglion, HSV-2 becomes latent in lumbar & sacral ganglion)
- During latency, most viral DNA is located in cytoplasm rather than integrated into nuclear DNA
- Virus can be reactivated from latent state by variety of inducers: sunlight, hormonal changes, trauma, stress, & fever, at which time it migrates down the neuron & replicates in the skin, causing lesions
Typical skin lesions of HSV is a?
- Vesicle that contains serous fluid filled with virus particles and cell debris. When the vesicle ruptures, the virus is liberated and can be transmitted to others.
- Multinucleated giant cells are typically found at the base of herpesvirus lesions
Immunity for HSV
- Type specific, some cross protection exists
- Immunity incomplete, both reinfection & reactivation occur in presence of circulating IgG
- Cell-mediated immunity important in limiting herpesviruses
HSV-1 Gingivostomatitis occurs?
- Primarily in children & characterized by fever, irritability, and vesicular lesions in mouth.
- Primary disease more severe and lasts longer than recurrences.
- Lesions heal spontaneously in 2-3 weeks
- Many children have asymptomatic primary infections
HSV-1 Herpes labialis (fever blisters or cold sores) is the?
- Milder recurrent form
- Characterized by crops of vesicles (mucocutanous junction of lips or nose
- Recurrences reappear at same time
HSV-1 Keratoconjunctivitis is? (2 points)
- Characterized by corneal ulcers & lesions of conjunctivae epithelium
- Recurrences can lead to scarring & blindness
HSV-1 Encephalitis is? (8 points)
- Characterized by necrotic lesion in one temporal lobe
- Fever, headache, vomiting, seizures, and altered mental status
- Onset may be acute or protracted over several days
- Disease occurs as a result of either primary infection or recurrence
- MRI imaging reveals lesion
- Exam of spinal fluid shows increase lymphocytes, elevation protein amount, normal glucose amount
- High mortality rate
- Severe neurologic sequelae in those who survive
HSV-1 Herpetic whitlow is a?
Pustular lesion of the skin of the finger or hand. Can occur in medical personnel as result of contact w/patients lesions
HSV-1 Herpes gladiatorum is?
- Occurs in wrestlers & others who have close body contacts
- Caused primarily by HSV-1
- Characterized by vesicular lesions on head, neck, & trunk
HSV-1 Disseminated infections are?
Such as esophagitis & pneumonia, occur in immunocompressed patients with depressed T-cell function
HSV-2 Genital herpes is?
- Characterized by painful vesicular lesions of the male/female genitals/anal area
- Lesions more severe & protracted in primary disease than in recurrences
- Primary infections are associated with fever, & inguinal adenopathy
- Asymptomatic infections occur in men (prostate or urethra) & women (cervix). Can be source of infection of other individuals
- Many infections asymptomatic
HSV-2 Neonatal herpes is?
- Originates from contact w/vesicular lesions w/in birth canal (some cases no visible lesions)
- Shed onto birth canal (asymptomatic shedding) can infect child during birth
- Varies from severe to mild local lesions to asymptomatic infections
- May be prevented by performing C section
- Both HSV-1 & 2 can cause severe neonatal infections that are acquired after birth from carriers handling the child
- Neither virus causes congenital abnormalities
Serious neonatal infection is more likely to occur when the mother is experiencing a primary herpes infection than a recurrent infection for two reasons
1) Amount of virus produced during primary infection is greater than recurrent
2) Mothers who have been previously infected can pass IgG across placenta, which can protect neonate from serious disseminated infection
Aseptic meningitis caused by HSV-2 is?
A mild self-limiting disease with few sequelae
Both HSV-1 & 2 are associated with erythema multiforme. This rash appears as a central red area surround by a ring (target or bulls eye lesion). Lesions are typically?
Mascular or papular & occur symmetrically on the trunk, hands, and feet.
- Rash though to be immune-mediated reaction to presence of HSV antigens
- Acyclovir useful in preventing recurrent episodes by reducing amount of HSV antigens
- Many drugs commonly cause erythema multiforme
Erythema multiforme major, also known as Stevens Johnson syndrome, is characterized by?
Fever, erosive oral lesions, and extensive desquamating skin lesions. M. pneumonia is most commonly caused by this.
What suggests a herpes virus infection?
The presence of multinucleated giant cells
Treatment for HSV-1 & 2
1) Acyclovir (acycloguanosine, Zovirax) treatment for encephalitis and system disease caused by HSV-1
* also useful for primary & recurrent genital herpes
* neonatal infections caused by HSV-2
* mutans of HSV-1 resistant have been isolated from patients
2) HSV-1 eye infections other nucleoside analogs used topically
3) No drug treatment of primary infection prevents recurrences, drugs have no effect on latent state, but prophylactic, long term administration of acyclovir, valacyclovir, or famcicylovir can suppress clinical recurrences
What does Acyclovir do for HSV-1 & 2?
It shortens the duration of lesions & reduces extent of shedding of the virus
Prevention of HSV-1 & 2
- Avoid contact w/vesicular lesion or ulcer
- C-section for women who are at term & who have genital lesions or positive viral cultures
- Circumcision reduces risk of infection
Comparison of diseases caused by HSV-1 & 2:
Skin
Mouth
Eye
Central nervous system
Neonate
Dissemination to viscera in immunocompressed patients
Skin: HSV-1: Vesicular lesions above waist HSV-2: Vesicular lesions below waist (genitals) Mouth: HSV-1: Gingivostomatitis HSV-2: Rare Eye: HSV-1: Keratoconjunctivitis HSV-2: Rare Central nervous system: HSV-1: Encephalitis (temporal lobe) HSV-2: Meningitis Neonate: HSV-1: Rare HSV-2: Skin lesions, encephalitis, disseminating infections Dissemination to viscera in immunocompressed patients: HSV-1: Yes HSV-2: Rare
What disease(s) does varicella-zoster virus cause?
Varicella (chickenpox) is the primary disease; zoster (shingles) is the recurrent form
Important properties of Varicella-zoster virus (VZV)
- Structurally & morphologically similar to others herpes viruses but is antigenically different.
- Has single serotype
- Same virus causes both varicella & zoster
- humans natural host
Replicative cycle of Varicella-zoster virus (VZV)
Similar to that of HSV
Transmission for Varicella-zoster virus
- Transmitted by respiratory droplets & by direct contact w/lesions
- Varicella is a highly contagious disease of childhood, more than 90% of people in US have antibody by age 10
- Varicella occurs worldwide
- Widespread use of vaccine has reduced number of cases
- Infectious VSV in zoster vesicles. This can be transmitted by direct contact to children & can cause varicella
- Appearance of either varicella or zoster in a hospital is major infection control problem because virus can be transmitted to immunocompressed patients & cause life-threatening disseminated infection
Pathogenesis & immunity for Varicella-zoster virus
- Infects mucosa of upper respiratory tract, then spreads via blood to the skin where vesicular rash occurs
- Multinucleated giant cells w/intranuclear inclusions are seen in base of lesions
- Virus infects sensory neurons & carried by retrograde axonal flow into cells of the dorsal root ganglion where virus becomes latent
- In latently infected cells VZV DNA is located in the nucleus & is not integrated into cellular DNA, later in life, at times of reduced cell-mediated immunity or local trauma, virus is activated & causes the vesicular skin lesions & nerve pain of zoster
- Immunity following varicella is lifelong, a person gets it once but zoster can occur despite immunity, zoster usually occurs once. Frequency of zoster increases w/advancing age
Clinical findings for varicella
- After incubation period (14-21 days), brief prodromal symptoms of fever & malaise occur
- Papulovesicular rash appears in crops on trunk & spreads to head & elsewhere
- Rash evolves from papules to vesicles then pustules & then crusts
- Itching symptom (vesicle present)
- Mild in children, severe in adults
- Varicella pneumonia & encephalitis are major rare complications (seen most in adults)
- Reye’s syndrome (encephalopathy & liver degeneration) associated w/VSV & influenza B virus infection (seen in children given aspirin)
Clinical findings for zoster virus
- Occurrence of painful vesicles along course of a sensory nerve of the head or trunk
- Pain can last for weeks
- Postzoster neuralgia can be debilitating
- Immunocompressed patients, life-threatening disseminated infections (pneumonia) can occur
Lab diagnosis for varicella-zoster
- Most made clinically, lab tests also available
- Presumption diagnosis made by using Tzanck smear
- Multinucleated giant cells seen in VZV as well as HSV lesions
- Definitive diagnosis made by isolation of virus in cell culture & identification w/specific antiserum
- Rise in antibody titer can be used to diagnose varicella but less useful in zoster
Treatment for varicella-zoster virus
- No antiviral therapy necessary in immunocompetent children
- Immunocompetent adults with either moderate or severe cases are treated w/acyclovir which reduces duration & severity of symptoms
- Immunocompressed children & adults w/chicken pox, zoster, or disseminated disease should be treated w/acyclovir
- Disease caused by acyclovir resistant strains of VZV treated w/foscarnet
- No drugs can cure latent state & none have any effect on postzoster neurglia
Prevention for Varicella-zoster virus
1) 2 vaccines against VZV:
* One designed to prevent varicella, other designed to prevent zoster
* Both contain live attenuated VZV, but zoster vaccine contains 14x more virus than varicella
2) Zoster vaccine effective in preventing zoster symptoms, but doesn’t eradicate latent state of VZV
3) Varicella vaccine recommended for children between 1-12yrs
4) Zoster vaccine recommended for older than 60yrs & who have had varicella
5) Because the vaccines contain live virus they should not be given to immunosuppressed people or pregnant
6) Acyclovir useful in preventing varicella & disseminated zoster in immunocompromised people exposed to virus
7) Varicella-zoster immune globulin (VZIG), which contains higher titer of antibody to virus also used
What diseases does cytomegalovirus cause?
- Cytomegalic inclusion disease (especially congenital abnormalities) in neonates
- Most common cause of congenital abnormalities in US
- Important cause of pneumonia & other diseases in immunocompromised patients (recipients of bone marrow,, solid organ transplants)
- Causes heterophilnegative mononucleosis in immunocompetent individuals
Important properties of cytomegalovirus
- Structurally & morphologically similar to herpesviruses but is antigenically different
- Single serotype
- Humans natural host
- Animal strains do not infect humans
- Giant cells are formed
Replicative cycle of cytomegalovirus
- Similar to that of HSV & VZV
- Unique feature: some immediate early proteins are translated from mRNAs brought into infected cell by parental virion rather than being translated from mRNAs synthesized in the newly infected cell
Transmission for cytomegalovirus
- Transmitted by variety of modes
- Early in life transmitted across placenta, w/in birth canal, breast milk
- In young children: saliva
- Sexually
- Present in both semen & cervical secretions
- Blood transfusions & organ transplants
- Occurs worldwide
- More than 80% adults have antibodies against virus
For cytomegalovirus, infection of the fetus can cause cytomegalic inclusion disease, characterized by multinucleated giant cells with prominent intranuclear inclusions. Describe this disease
- Many organs affected & widespread congenital abnormalities result
- Infection of fetus occurs when primary infection occurs in pregnant women (when she has no antibodies that will neutralized the virus before it can infect the fetus)
- Fetus won’t be infected if mom has antibody
- Congenital abnormalities are common when a fetus is infected during 1st trimester than later gestation, because the 1st trimester is when development of organs occurs & the death of any precursor cells can result in congenital defects
Describe the infections in children and adults for cytomegalovirus
- Usually asymptomatic (except immunocompromised)
- CMV enters latent state in leukocytes & reactivated when cell mediated immunity is decreased
- Can persist in kidneys for years
- Reactivation from latent state in cervical cells can result in infection of newborn during passage through birth canal
Cytomegalovirus has a specific mechanism of immune evasion that allows it to maintain the latent state for long periods. Explain
Assembly of the MHC class-I viral peptide complex is unstable, viral antigens not display on cell surface & killing by cytotoxic T cells does not occur. Encodes several microRNAs, one of which binds to and prevents translation of the cells mRNA for class-I MHC protein. This prevents viral proteins from being displayed on the infected cell surface & killing by cytotoxic T cells does not occur
Cytomegalovirus infection causes an immunosuppressive effect by inhibiting T-cells. Host defenses against CMV infection include?
Both circulating antibody and cell-mediated immunity. Cellular immunity is more important because its suppression can lead to systemic disease
Approximately 20% of infants infected with cytomegalovirus during gestation show clinically apparent manifestations of cytomegalic inclusion disease such as?
- Microcephaly, seizures, deafness, juandice, & purpura
- Hepatospleomegaly is common
- Cytomegalic inclusion disease one of leading causes of mental retardation in US
- Infected infants continue to excrete CMV, especially in urine, for several years
In immunocompetent adults cytomegalovirus can cause heterophilnegative mononucleosis, which is?
Characterized by fever, lethargy, & presence of abnormal lymphocytes in peripheral blood smears
Systemic cytomegalovirus infections, especially pneumonoitis & hepatitis occurs?
In a high proportion of immunosupressed patients (those with renal & bone marrow transplants). In AIDS patients CMV commonly infects the intestinal tract & cause intractable colitis w/diarrhea. Also causes retinitis in AIDS patients which can lead to blindness
Treatment for cytomegalovirus
- Ganciclovir (cytovene) moderately effective in treatment of retinitis & pneumonia in patients w/AIDS. Valganciclovir which can be taken orally, also effective
- Resistance to ganciclovir & valganciclovir have emerged due to mutations in UL97 gene that encodes phosphokinase
- Drug susceptibility testing can be done
- Foscarnet also effective but causes more side effects
- Unlike HSV, & VZV, CMV is resistant to acyclovir
- Vistide also useful for treatment in CMV retinitis
Prevention for cytomegalovirus
- No vaccine
- Ganciclovir can suppress progressive retinitis in AIDS pateints
- Infants w/cytomegalic inclusion disease who are shedding virus in their urine should be kept isolated from other infants
- Blood for transfusion to newborns should be CMV antibody-negative
- If possible, only organs from CMV antibody-negative recipients
- High titer immune-globulin preparation (CytoGam) is used to prevent disseminated infections in organ transplant patients
What diseases does Epstein Barr virus cause?
Infectious mononucleosis. Associated w/Burkitt’s lymphoma, other B cell lymphomas, & nasopharyngeal carcinoma. Also causes hairy leukoplakia
Important properties of Epstein Barr virus
- Structurally and morphologically similar to other herpesvirues but is antigenically different
- Most important antigen is viral capsid antigen (VCA), used most often in diagnostic tests
- Early antigens (EA) are produced prior to viral DNA synthesis & nuclear antigen (EBNA), which is located in the nucleus bound to chromosomes, sometimes diagnostically helpful
- Also detected antigens are; lymphocyte-determined membrane antigen & viral membrane antigen
- Neutralizing activity directed against the viral membrane antigen
- Humans natural host
- Infects mainly lymphoid cells primarily B lymphocytes
- In latently infected cells EBV DNA is in the nucleus & is not integrated into cellular DNA
- Some (not all) genes are transcribed & only subset of these are translated to protein
Replicative cycle for Epstein-Barr virus
Similar to that of HSV. EBV enters B lymphocytes at the site of the receptor for the C3 component of compliment
How is Epstein-Barr transmitted?
1) Primarily by exchange of saliva (kissing)
- Saliva of people w/a reactivation of a latent infection as well as w/an active infection can serve as source
2) Blood transmission rare
3) One of most common infections worldwide
- More than 90% adults in US have antibody
4) Infection in first few years of life usually asymptomatic
- Early infection tends to occur in individuals in lower socioeconomic groups
5) Frequency of clinically apparent infectious mononucleosis is highest in those who are exposed to virus later in life (college)
The infection of Epstein-Barr first occurs in the?
Oropharynx & then spread to the blood, where it infects B lymphocytes. Cytotoxic T lymphocytes react against the infected B cells. The T cells are the atypical lymphs seen in the blood smear. EBV remains latent w/in B lymphocytes
Describe the immune response to the Epstein-Barr virus
1) Consists 1st of IgM antibody to the VCA
2) IgG antibody to the VCA follows & persists for life
3) IgM response is therefore useful for diagnosing acute infection, IgG response best for revealing prior infection
4) Lifetime immunity against second episodes of infectious mononucleosis is based on antibody to the viral membrane antigen
In addition to the Epstein-Barr virus specific antibodies, nonspecific heterophil antibodies are found. The term “heterophil” refers to?
- Antibodies that are detected by tests using antigens different from the antigens that induced them.
- The heterophil antibodies formed in infectious mononucleosis agglutinate sheep or horse red blood cells in the lab
Infectious mononucleosis caused by Epstein-Barr virus is characterized primarily by?
- Fever, sore throat, lymphadenopathy, & splenomegaly. Anorexia & lethargy are prominent
- Hepatitis is frequent; encephalitis occurs in some patients
- Spontaneous recovery usually occurs in 2 to 3 weeks
- Splenic rupture, associated w/contact sports such as football, is a feared but rare complication of the splenomegaly
Epstein-Barr virus also causes a severe, often fatal what?
Progressive form of infectious mononucleosis that occurs in children with an inherited immunodeficiency called X-linked lymphoproliferative syndrome. The mutated gene encodes a signal transduction protein required for both T-cell & NK cell function.
- Mortality rate 75% by 10yrs
- Bone marrow or cord blood transplants may cure the underlying immunodeficiency
