Virus
Organism Herpes simplex virus-1 (HSV-1)
Disease Herpes – acute gingivostomatitis, recurrent herpes labialis (cold sores), keratoconjunctivitis (keratitis) & encephalitis
Morphology Herpesviruses – Double stranded (ds) DNA enveloped virus (along w poxvirus) & hepadnaviruses
Icosahedral core w lipoprotein envelope
X polymerase
Epidemiology Most occurs during childhood
MOT Saliva & asymptomatic shedding
Life cycle Replicate in skin/mucous membrane
HSV-1 binds to heparan sulfate on cell surface then nectin receptor
➢ Fusion w cell membrane
➢ Protein release into cytoplasm
Viral nucleocapsid transported to nucleus
➢ VP-16 activate transcription of viral IE gene
➢ IE protein later activate synthesis of DNAP & thymidine kinase
Pathogenesis Progeny virus infects adjacent neurons & migrates up axon by retrograde axonal flow to neuron nucleus – viral DNA x integrate into human DNA but remain as episome in
nucleus
➢ HSV become latent in sensory ganglion cells
➢ HSV-1 specifically at trigeminal ganglia
Virus reactivated from latent by inducers
➢ Virus migrate down neuron
➢ Replicate in skin causing lesions
Vesicles w serous fluid w viral particles – multinucleated giant cell at base of lesion
➢ Progress to erythema → papules → ulcers → crust
➢ Prodromal itching/tingling can occurs
S&S Painful vesicle lesions generally above waist (mainly on face)
➢ Gingivostomatitis – fever, irritability, vesicles (self-limiting)
➢ Orolabial herpes
➢ Keratoconjunctivitis – corneal ulcers → scarring & blindness
➢ Encephalitis – (necrotic lesion in temporal lobe) headache, vomiting, seizure, altered mental status
➢ Herpetic whitlow – pustular lesion
➢ Herpes gladiatorum
➢ Eczema herpeticum/Kaposi varicelliform eruption
➢ Disseminated infection – esophagitis, pneumonia in IC
➢ Erythema multiforme/Steven Johnson syndrome – allergic reaction to infection/drugs, bull-eye lesion (macular/popular) symmetrically on trunk, hands & feet
Complication Lifelong latent infection
Blindness
Encephalitis
Dx PCR (more common)
NAAT
Viral culture
Skin lesion scrap under Tzanck smear
Direct fluorescent antibody (DFA) test
Diff Dx HSV-2
Tx Acyclovir (DOC)
Penciclovir/docosanol – recurrent in IC
Prevention Avoid contact
X vaccine
Organism Herpes simplex virus-2 (HSV-2)
Disease Herpes – genital herpes, neonatal encephalitis & aseptic meningitis (no pus)
Morphology Herpesviruses, icosahedral core w lipoprotein envelope, x polymerase
Epidemiology Commonly after puberty
Recurrences is more common
MOT Sexual contact
Asymptomatic shedding
RF ➢ Promiscuous
Life cycle = as HSV-1
Pathogenesis = as HSV-1, however: -
➢ HSV-2 stays latent especially in the lumbar & sacral ganglion
S&S Painful vesicular lesion below the waist (now due to oral-genital practice S & S on mouth too)
➢ Erythema multiform/Steven Johnson syndrome
➢ Genital herpes – painful vesicular lesion (more severe in 1* disease), fever & inguinal adenopathy
➢ Neonatal herpes – mild local lesion to asymptomatic
➢ Aseptic meningitis – mild, self-limiting disease w few sequelae
Dx = as HSV-1
Tx Acyclovir
Prevention Valacyclovir/famciclovir – recurrence suppression
C-section for infected mothers
Circumcision
Organism Varicella zoster virus (VZV)
Disease Varicella / chickenpox
Zoster / shingles – recurrent infection
Morphology Herpesviruses
Single serotype
MOT Respiratory droplets / direct contact w lesion
RF ➢ IC
Life cycle = to HSV
,Pathogenesis Infection URT mucosa
➢ Spread to skin via blood
Typical vesicular rash occurs (multinucleated giant cell w intranuclear inclusion at base of lesion)
➢ Virus infect sensory neurons & retrograde axonal flow into dorsal root ganglia
Here the virus become latent
➢ Reactivated due to inducers
Vesicular skin lesions & nerve pain of zoster
S&S Varicella
➢ Fever & malaise
➢ Papulovesicular rash on trunks & spread to head & extremities
➢ Rash → papules → vesicles → pustules → crust
➢ Pruritus on vesicles
Zoster
➢ Painful vesicles along sensory nerve of head/trunk
➢ Postherpetic neuralgia (PNH)
Complication Varicella pneumonia & encephalitis
Reye’s syndrome – encephalopathy & liver degeneration
Dx PCR
DFA
Tzanck smear
Viral culture
Serological test
Tx X antiviral
Acyclovir to ↓symptoms prior to symptoms manifestation
Foscarnet – acyclovir resistant strain
Analgesic for PNH
Prognosis Immunity is lifelong w infection only occurring once in a lifetime
Prevention 2 vaccines
➢ Variva – prevent varicella (live, attenuated)
For >1Y
➢ Shingrix – prevent shingles (recombinant w envelope glycoprotein)
For any age
Varicella zoster immune globulin for chemoprophylaxis
Organism Cytomegalovirus (CMV)
Disease Cytomegalic inclusion disease, congenital abnormalities, heterophil-negative mononucleosis
Morphology Herpesviruses
Single serotype with many genotype
Virulence Anti-HLA class 1 protein – prevent CD8+ cell from killed CMV infected cells
MicroRNA – prevent translation of class I MHC protein
Chemokine receptor like protein – binds to chemokines & prevent signal for immune cell to migrate to infection site
Immunosuppressive effect – inhibit T cells
Epidemiology Most common cause of congenital abnormalities
Congenital abnormalities more common during the 1st trimester
MOT ➢ Thru placenta
➢ Vertical transmission
➢ Breast milk
➢ Saliva
➢ Sexually transmitted
➢ Blood transfusion
➢ Organ transplant
Usually asymptomatic exp IC
Life cycle = to HSV
Pathogenesis Fetal infection cause cytomegalic inclusion disease
➢ Multinucleated giant cell w intracellular inclusion
CMV enters into latent stage in monocytes, kidneys & reactivated when ↓CMI
S&S Congenital abnormalities in infant: -
➢ Microcephaly
➢ Seizure
➢ Deafness
➢ Jaundice
➢ Purpura – blue berry muffin lesion
➢ Hepatosplenomegaly
➢ Mental retardation
Adults: -
➢ Heterophil negative mononucleosis (fever, lethargy, abnormal lymphocytes in peripheral blood smear)
IC: -
➢ Pneumonitis
➢ Esophagitis
➢ Hepatitis
➢ Intractable colitis
➢ Retinitis → blindess
➢ Anemia & thrombocytopenia
Dx PCR for CMV DNA/viral mRNA
Culture in shell vials w IF Ab
IF Ab & histologic staining – giant cells w owl eye inclusion bodies
Serological IgM test
Tx Ganciclovir - IC & AIDs
Valganciclovir - CMV retinitis
Foscarnet – resistant strain
Prevention X vaccine
Ganciclovir for suppression
, Infected infant isolated
Organism Epstein Barr Virus (EBV)
Disease Infectious mononucleosis, Burkitt’s lymphoma, B-cell lymphomas, nasopharyngeal CA, hairy leukoplakia, post-transplant lymphoproliferative disorder (PTLD) &
hemophagocytic lymphohistiocytosis (HLH)
Morphology Herpesviruses
Has viral capsid Ag (VCA)
Epidemiology Commonly in low SES
MOT ➢ Saliva
Usually asymptomatic (early stage)
Life cycle = to HSV
Enter B-lymphocytes at C3 receptor
Pathogenesis Infection lymphoid, pharynx epithelial cells
➢ Spread to blood & infect B-lymphocytes
➢ Remain latent in cell
Immune response to VCA
S&S Infectious mononucleosis
➢ Fever
➢ Sore throat
➢ Lymphadenopathy
➢ Splenomegaly
➢ Anorexia & lethargy
➢ Hepatitis
➢ Encepahlitis
Hairy leukoplakia (common in IC)
➢ Whitish
➢ Non-malignant lesion w irregular hairy surface on lat side of tongue
Complication X-linked lymphoproliferative syndrome
➢ Children w this inherited immunodeficiency gets fatal infectious mononucleosis if infected w EBV
PTLD is due to B-cell lymphoma following bone marrow/organ transplant
HLH affects children
➢ Fever
➢ Hepatosplenomegaly
➢ Cytopenias
Dx Serology test – IgM VCA
EVB specific Ab test
Monospot test – detect heterophil Ab (<common)
Blood examination
➢ Absolute lymphocytosis
➢ Atypical lymph w expanded nucleus & abundant vacuolated cytoplasm
PCR
Tx X antiviral
Prevention X vaccine
Organism Human Herpes virus-6 (HHV-6)
Disease Roseola infantum (exanthem subitem)
Morphology Herpesviruses
Epidemiology Common in children
Encephalitis common in patient receiving stem-cell transplant
Pathogenesis Lymphotropic infecting both T & B cells
➢ Remain latent & reactivate during times of ↓CMI
S&S ➢ Sudden high fever
➢ When fever is gone – transient macular/maculopapular erythematous rash on face & trunk
In IC: -
➢ Pneumonitis
➢ Encephalitis
➢ Hepatitis
Dx PCR for viral DNA - ↑>x4 rise in Ab
Tx X antiviral
Ganciclovir for IC
Prevention X vaccine
Organism HHV-8
Disease Kaposi sarcoma, 1* effusion lymphoma, multimeric Castleman disease & inflammatory cytokine syndrome asso w HIV
Morphology Herpesviruses
6 main subtypes in different geographical regions
Virulence Latency associated nuclear Ag (LANA) – inhibit p53 gene transcription
Cyclin D viral gene – overrides cell cycle growth
Protein gene – inhibit Fas death pathway allowing infected cell to attach CD8+ cell
Epidemiology KS is most common cancer asso w HIV
MOT ➢ Saliva
➢ Sexual intercourse
➢ Organ transplant
Life cycle Both lytic & latent cycle
➢ Lytic produce infective virus
➢ Latent involve in malignant transformation
Pathogenesis Malignancy of vascular endothelial cells
➢ Many spindle shaped cell & RBC
HHV-8 first inactivate TSG by producing LANA inactivating p53
➢ Resulting in malignant transformation
Organism Herpes simplex virus-1 (HSV-1)
Disease Herpes – acute gingivostomatitis, recurrent herpes labialis (cold sores), keratoconjunctivitis (keratitis) & encephalitis
Morphology Herpesviruses – Double stranded (ds) DNA enveloped virus (along w poxvirus) & hepadnaviruses
Icosahedral core w lipoprotein envelope
X polymerase
Epidemiology Most occurs during childhood
MOT Saliva & asymptomatic shedding
Life cycle Replicate in skin/mucous membrane
HSV-1 binds to heparan sulfate on cell surface then nectin receptor
➢ Fusion w cell membrane
➢ Protein release into cytoplasm
Viral nucleocapsid transported to nucleus
➢ VP-16 activate transcription of viral IE gene
➢ IE protein later activate synthesis of DNAP & thymidine kinase
Pathogenesis Progeny virus infects adjacent neurons & migrates up axon by retrograde axonal flow to neuron nucleus – viral DNA x integrate into human DNA but remain as episome in
nucleus
➢ HSV become latent in sensory ganglion cells
➢ HSV-1 specifically at trigeminal ganglia
Virus reactivated from latent by inducers
➢ Virus migrate down neuron
➢ Replicate in skin causing lesions
Vesicles w serous fluid w viral particles – multinucleated giant cell at base of lesion
➢ Progress to erythema → papules → ulcers → crust
➢ Prodromal itching/tingling can occurs
S&S Painful vesicle lesions generally above waist (mainly on face)
➢ Gingivostomatitis – fever, irritability, vesicles (self-limiting)
➢ Orolabial herpes
➢ Keratoconjunctivitis – corneal ulcers → scarring & blindness
➢ Encephalitis – (necrotic lesion in temporal lobe) headache, vomiting, seizure, altered mental status
➢ Herpetic whitlow – pustular lesion
➢ Herpes gladiatorum
➢ Eczema herpeticum/Kaposi varicelliform eruption
➢ Disseminated infection – esophagitis, pneumonia in IC
➢ Erythema multiforme/Steven Johnson syndrome – allergic reaction to infection/drugs, bull-eye lesion (macular/popular) symmetrically on trunk, hands & feet
Complication Lifelong latent infection
Blindness
Encephalitis
Dx PCR (more common)
NAAT
Viral culture
Skin lesion scrap under Tzanck smear
Direct fluorescent antibody (DFA) test
Diff Dx HSV-2
Tx Acyclovir (DOC)
Penciclovir/docosanol – recurrent in IC
Prevention Avoid contact
X vaccine
Organism Herpes simplex virus-2 (HSV-2)
Disease Herpes – genital herpes, neonatal encephalitis & aseptic meningitis (no pus)
Morphology Herpesviruses, icosahedral core w lipoprotein envelope, x polymerase
Epidemiology Commonly after puberty
Recurrences is more common
MOT Sexual contact
Asymptomatic shedding
RF ➢ Promiscuous
Life cycle = as HSV-1
Pathogenesis = as HSV-1, however: -
➢ HSV-2 stays latent especially in the lumbar & sacral ganglion
S&S Painful vesicular lesion below the waist (now due to oral-genital practice S & S on mouth too)
➢ Erythema multiform/Steven Johnson syndrome
➢ Genital herpes – painful vesicular lesion (more severe in 1* disease), fever & inguinal adenopathy
➢ Neonatal herpes – mild local lesion to asymptomatic
➢ Aseptic meningitis – mild, self-limiting disease w few sequelae
Dx = as HSV-1
Tx Acyclovir
Prevention Valacyclovir/famciclovir – recurrence suppression
C-section for infected mothers
Circumcision
Organism Varicella zoster virus (VZV)
Disease Varicella / chickenpox
Zoster / shingles – recurrent infection
Morphology Herpesviruses
Single serotype
MOT Respiratory droplets / direct contact w lesion
RF ➢ IC
Life cycle = to HSV
,Pathogenesis Infection URT mucosa
➢ Spread to skin via blood
Typical vesicular rash occurs (multinucleated giant cell w intranuclear inclusion at base of lesion)
➢ Virus infect sensory neurons & retrograde axonal flow into dorsal root ganglia
Here the virus become latent
➢ Reactivated due to inducers
Vesicular skin lesions & nerve pain of zoster
S&S Varicella
➢ Fever & malaise
➢ Papulovesicular rash on trunks & spread to head & extremities
➢ Rash → papules → vesicles → pustules → crust
➢ Pruritus on vesicles
Zoster
➢ Painful vesicles along sensory nerve of head/trunk
➢ Postherpetic neuralgia (PNH)
Complication Varicella pneumonia & encephalitis
Reye’s syndrome – encephalopathy & liver degeneration
Dx PCR
DFA
Tzanck smear
Viral culture
Serological test
Tx X antiviral
Acyclovir to ↓symptoms prior to symptoms manifestation
Foscarnet – acyclovir resistant strain
Analgesic for PNH
Prognosis Immunity is lifelong w infection only occurring once in a lifetime
Prevention 2 vaccines
➢ Variva – prevent varicella (live, attenuated)
For >1Y
➢ Shingrix – prevent shingles (recombinant w envelope glycoprotein)
For any age
Varicella zoster immune globulin for chemoprophylaxis
Organism Cytomegalovirus (CMV)
Disease Cytomegalic inclusion disease, congenital abnormalities, heterophil-negative mononucleosis
Morphology Herpesviruses
Single serotype with many genotype
Virulence Anti-HLA class 1 protein – prevent CD8+ cell from killed CMV infected cells
MicroRNA – prevent translation of class I MHC protein
Chemokine receptor like protein – binds to chemokines & prevent signal for immune cell to migrate to infection site
Immunosuppressive effect – inhibit T cells
Epidemiology Most common cause of congenital abnormalities
Congenital abnormalities more common during the 1st trimester
MOT ➢ Thru placenta
➢ Vertical transmission
➢ Breast milk
➢ Saliva
➢ Sexually transmitted
➢ Blood transfusion
➢ Organ transplant
Usually asymptomatic exp IC
Life cycle = to HSV
Pathogenesis Fetal infection cause cytomegalic inclusion disease
➢ Multinucleated giant cell w intracellular inclusion
CMV enters into latent stage in monocytes, kidneys & reactivated when ↓CMI
S&S Congenital abnormalities in infant: -
➢ Microcephaly
➢ Seizure
➢ Deafness
➢ Jaundice
➢ Purpura – blue berry muffin lesion
➢ Hepatosplenomegaly
➢ Mental retardation
Adults: -
➢ Heterophil negative mononucleosis (fever, lethargy, abnormal lymphocytes in peripheral blood smear)
IC: -
➢ Pneumonitis
➢ Esophagitis
➢ Hepatitis
➢ Intractable colitis
➢ Retinitis → blindess
➢ Anemia & thrombocytopenia
Dx PCR for CMV DNA/viral mRNA
Culture in shell vials w IF Ab
IF Ab & histologic staining – giant cells w owl eye inclusion bodies
Serological IgM test
Tx Ganciclovir - IC & AIDs
Valganciclovir - CMV retinitis
Foscarnet – resistant strain
Prevention X vaccine
Ganciclovir for suppression
, Infected infant isolated
Organism Epstein Barr Virus (EBV)
Disease Infectious mononucleosis, Burkitt’s lymphoma, B-cell lymphomas, nasopharyngeal CA, hairy leukoplakia, post-transplant lymphoproliferative disorder (PTLD) &
hemophagocytic lymphohistiocytosis (HLH)
Morphology Herpesviruses
Has viral capsid Ag (VCA)
Epidemiology Commonly in low SES
MOT ➢ Saliva
Usually asymptomatic (early stage)
Life cycle = to HSV
Enter B-lymphocytes at C3 receptor
Pathogenesis Infection lymphoid, pharynx epithelial cells
➢ Spread to blood & infect B-lymphocytes
➢ Remain latent in cell
Immune response to VCA
S&S Infectious mononucleosis
➢ Fever
➢ Sore throat
➢ Lymphadenopathy
➢ Splenomegaly
➢ Anorexia & lethargy
➢ Hepatitis
➢ Encepahlitis
Hairy leukoplakia (common in IC)
➢ Whitish
➢ Non-malignant lesion w irregular hairy surface on lat side of tongue
Complication X-linked lymphoproliferative syndrome
➢ Children w this inherited immunodeficiency gets fatal infectious mononucleosis if infected w EBV
PTLD is due to B-cell lymphoma following bone marrow/organ transplant
HLH affects children
➢ Fever
➢ Hepatosplenomegaly
➢ Cytopenias
Dx Serology test – IgM VCA
EVB specific Ab test
Monospot test – detect heterophil Ab (<common)
Blood examination
➢ Absolute lymphocytosis
➢ Atypical lymph w expanded nucleus & abundant vacuolated cytoplasm
PCR
Tx X antiviral
Prevention X vaccine
Organism Human Herpes virus-6 (HHV-6)
Disease Roseola infantum (exanthem subitem)
Morphology Herpesviruses
Epidemiology Common in children
Encephalitis common in patient receiving stem-cell transplant
Pathogenesis Lymphotropic infecting both T & B cells
➢ Remain latent & reactivate during times of ↓CMI
S&S ➢ Sudden high fever
➢ When fever is gone – transient macular/maculopapular erythematous rash on face & trunk
In IC: -
➢ Pneumonitis
➢ Encephalitis
➢ Hepatitis
Dx PCR for viral DNA - ↑>x4 rise in Ab
Tx X antiviral
Ganciclovir for IC
Prevention X vaccine
Organism HHV-8
Disease Kaposi sarcoma, 1* effusion lymphoma, multimeric Castleman disease & inflammatory cytokine syndrome asso w HIV
Morphology Herpesviruses
6 main subtypes in different geographical regions
Virulence Latency associated nuclear Ag (LANA) – inhibit p53 gene transcription
Cyclin D viral gene – overrides cell cycle growth
Protein gene – inhibit Fas death pathway allowing infected cell to attach CD8+ cell
Epidemiology KS is most common cancer asso w HIV
MOT ➢ Saliva
➢ Sexual intercourse
➢ Organ transplant
Life cycle Both lytic & latent cycle
➢ Lytic produce infective virus
➢ Latent involve in malignant transformation
Pathogenesis Malignancy of vascular endothelial cells
➢ Many spindle shaped cell & RBC
HHV-8 first inactivate TSG by producing LANA inactivating p53
➢ Resulting in malignant transformation
