Viruses Flashcards
basic unit from which capsids are built
structural unit
protomer
surface structures seen by EM
morphological unit
capsomer
protein shell surrounding the nucleic acid genome
capsid
coat
lipid bilayer derived from host membrane carrying viral glycoprotein
envelop
viral membrane
complete infectious virus particle
virion
nucleic acid core (genome), core proteins, and capsid (protein coat)
nucleocapsid
capsid type
assembly of nucleocapsid requires the presence of nucleic acid
each protomer interacts directly with nucleic acid
size of the nucleocapsid is limited by the amount of nucleic acid enclosed
helical capsids
capsid type
nucleic acid is notneeded for capsid formation (empty capsid forms)
size of the capsid limits the amount of nucleic acid enclosed
multiple proteins are usually involved in forming the capsid
icosahedral capsid
capsid type
poxviruses
DNA viruses carries machineries for cytoplasmic replication (replication enzymes)
virions are very sable (6 months) even when desiccated and at room temperature
complex virion
viral genome directly translatable into protein, acts as mRNA
Positive sense RNA genome
viral genome from which mRNA is made and translated into proteins
Negative sense RNA genome
pattern of viral disease
infection and complete recovery
acute infection
pattern of viral disease
final disease is different from initial disease
acute infection, rare late complication
pattern of viral disease
second disease episode is the same as the first; no infectious virus between episodes
latent infection
pattern of viral disease
following initial disease episode, virus is shed without overt disease
chronic infection
pattern of viral disease
virus is produced and shed for long period before disease manifests
chronic infection, late disease
amount of virus increases over time until sufficient level is reached to cause disease
slow infection
virus family 10-12 segments in dsRNA genome non-enveloped, icosahedral capsid Coltivirus - Colorado Tick Fever Rotavirus
Reoviruses
most important cause of severe diarrhea in children under 5 worldwide (most common in 6-24 months)
outbreaks in child care centers, nosocomial infections in children’s hospitals
increased viral survival at higher humidity, peak incidence in cooler months
resists inactivation by concentration of chlorine used in treating sewage and drinking water
fever/vomiting for 2-3 days, progress to diarrhea for 4-8 days
watery profuse diarrhea, abdominal pain, severe volume depletion (dehydration)
seizures with aspiration of vomitus
chronic diarrhea in the immunocompromised
clinical diagnosis; ELISA, stool viral culture, stool EM, Latex agglutination, PCR
supportive care, no antivirals, hygiene, inactivation with 95% ethanol
RotaShield = oral, live attenuated vaccine, no longer available, causes intussusception
RotaTeq and Ratarix = oral, live attenutated vaccine, small risk of intussusception
non-enveloped, iscosahedral
11 dsRNA segments
triple layer structure: outercapsid (VP4, VP7), middle capsid (VP6, target of Ab), inner capsid (VP2, structure)
polymerase (VP1, transcription), guanyltransferase (VP3, RNA capping)
7 antigenic groups (Group A causes most human disease)
fecal-oral transmission; sloughing of enterocytes in stool results from receptor mediated endocytosis causing enterocyte infection and conversion to dual layer structure; viral replication produces new dual layer structures that obtain the third layer in the ER; progeny released by cell lysis
Rotavirus
virus family
nonsegmented +ssRNA genome
non-enveloped, icosahedral
worldwide distribution, affects all ages
occurs year round but is more common in less humid months/winter
associated with epidemic outbreaks of waterborne, foodborne, and shellfish-associated gastroenteritis
Norovirus
Caliciviridae
leading cause of food-borne disease outbreaks worldwide
Genetic mutation and recombination contribute to broad heterogeneity and emergence of new strains resulting in antigenic drift (especially genotype II)
Immunity is incomplete and temporary
Genotype GII.4 is responsible for 70-80% of outbreaks worldwide
VP1 is the major capsid protein; receptor binding region and major site of antigenic variation
Individual human susceptibility is related to the presence of specific histo-blood group antigens (secretor status); these are glycans on the surface of gut epithelial cells (polymorphic fucosyltransferase genes)
O negative individuals are resistant to infection
Frequently reported on ocean liners; transmission is linked to sewage contamination, poor water storage/ filtration/ chlorination, food handler carriage, food preparation/storage; also seen in hospitals, military camps, jails, and schools
rapid onset of symptoms and brief clinical course
Fever, anorexia, explosive watery diarrhea, forceful vomiting
Respiratory symptoms in 1/3 of children
Illness begins 12hr to 4 days after exposure and lasts 3-7 days
Diagnosis by clinical manifestations and PCR of stool, treatment is supportive
Norovirus
Norwalk virus
virus family linear ssRNA genome icosahedral, non-enveloped stable at pH 3-10 (survive stomach acid) replicate in the GIT and pharynx resistant to chloroform and alcohol shed from GIT more than URT cause minor and major viremia Enteroviruses
Picornaviridae
Enterovirus
Three serotypes; humans are the only natural host
life-long immunity, no cross-immunity with other serotypes
fecal-oral transmission
replication in the gut, dissemination to the RER via minor viremia, rare major viremia spread to other organs (muscle and brain)
biphasic
90-95% of infections are asymptomatic
abortive infection: fever, headache, sore throat, anorexia, indistinguishable from other viral infections
non-paralytic infection: aseptic meningitis similar to other enteroviruses, signs of meningeal irritation
paralytic infection: flaccid paralysis resulting from lower motor neuron damage; asymmetric, proximal muscles most affected, loss of reflexes but sensation intact; residual deficit in most
replication in the anterior horn cells of the spinal cord leads to spinal infection
involvement of the medulla and brain stem causes bulbar infection that leads to cranial nerve paralysis
involvement of the cortex causes encephalitic infection
Respiratory failure is responsible for most deaths (weakness of diaphragm and intercostals, involvement of respiratory center in brainstem, CN infection)
Post-infection syndrome is a late manifestation of acute paralytic infection in childhood; characterized by muscle pain and exacerbation of paralysis resulting from late attrition of oversized motor units that developed in the recovery process
Dx: viral isolation from throat, feces; serology
Occurred most often in the summer and fall in the US but can occur year round in tropic areas
Pre-industrial era: milder endemic form in infants protected by maternal antibodies
20th century: improved hygiene, epidemics in older children peaked in 1952; vaccine in 1955 resulted in sharp decline
Salk vaccine: (IPV) inactivated virus; mix of three types inactivated by formalin; currently used in most of Europe, US, and Canada
Sabin vaccine: (OPV) oral, leads to the additional development of mucosal immunity; used in developing countries; vaccine derived infection (if population is underimmunized, cVDPV)
Problems with eradication: subclinical cases, vaccine associated infections, changes in world populations/politics, long duration of eradication programs
Vaccine derived viruses can cause paralytic infection, potential for sustained circulation; can cause outbreaks in areas with low OPV coverage; OPV replaced with IPV in US; new cases in only 2 countries (Pakistan, Afghanistan)
Poliovirus
Non-polio enterovirus
Acquired by ingestion of virus shed in feces or URT
Replication in lymphoid tissues of the ileum gives rise to transient minor viremia and RES involvement
Major viremia seeds other target organs (CNS [meningitis], heart [myocarditis], skin [viral exanthema])
Infants and young children have the highest rates of infection and disease
Most infections are asymptomatic but some develop nonspecific febrile illness (lethargy, poor feeding, vomiting, and diarrhea)
Exanthema = rash resembling measles and rubella;
herpangina, hand-foot-mouth disease, acute hemorrhage conjunctivitis
Diagnosis by viral isolation in cell culture and PCR; serology can be done but there is cross-reactivity
Infection is usually self-limited and do not require treatment; in severe infection, Ig therapy has been used
Coxsackie viruses A
Non-polio enterovirus
Acquired by ingestion of virus shed in feces or URT
Replication in lymphoid tissues of the ileum gives rise to transient minor viremia and RES involvement
Major viremia seeds other target organs (CNS [meningitis], heart [myocarditis], skin [viral exanthema])
Infants and young children have the highest rates of infection and disease
Most infections are asymptomatic but some develop nonspecific febrile illness (lethargy, poor feeding, vomiting, and diarrhea)
Exanthema = rash resembling measles and rubella;
Aseptic meningitis, myocarditis and pleurodynia
Diagnosis by viral isolation in cell culture and PCR; serology can be done but there is cross-reactivity
Infection is usually self-limited and do not require treatment; in severe infection, Ig therapy has been used
Coxsackie virus B
virus family
enveloped ssRNA genome
bud from cell surface with embedded surface proteins
attachment to cell surface glycoproteins via hemagglutinin-neuraminidase, hemagglutinin, or G proteins
F protein mediated fusion of virus to host cell
Parainfluenza, mumps, measles, respiratory syncytial virus, metaneumovirus
Paramyxovirus
Morbillivirus; ssRNA virus
Hemagglutinin attaches to cell surface
predominantly a childhood illness, humans are the only hosts
seen worldwide, mostly in winter/spring
US cases largely due to importation
highly contagious, droplet spread by infected nasopharyngeal secretions
infects epithelial cells of respiratory tract, spread by viremia to RES, followed by secondary viremia
replication in conjunctiva, respiratory tract, GI, GU, lymphatics, blood vessels, and CNS
disease manifestations due to T-cell response to virus infected cells lining capillaries
multi-nucleated giant cells in skin, mucosa
Koplik’s spots = mucosal enenthem
maculopapular rash initially on face, spreads to trunk and limbs; confluent
complications: pneumonia, bacterial superinfection, encephaltits, subacute sclerosing panencephalitis
Dx: clinical appearance, serology, PCR
Tx: supportive, vitamin A
vaccine: MMR, two doses
Measles
Rubeola
endemic worldwide
US outbreaks related to importation from UK
humans are the only host
transmitted by direct contact, droplets, fomites
prodromal low grade fever, malaise, headache (flu-like)
progresses to earache and tenderness with parotid palpation
bilateral parotid enlargement
post-pubertal epididymo-orhcitis, meningitis, encelphalitis are possible
vaccine preventable (MMR), some evidence of lost immunity with time
Mumps
major cause of lower respiratory tract infection in young children; also seen in immunocompromised adults
primarily in winter and spring
outbreaks last up to 20 weeks
all children are infected in the first few years of life
inoculation through nose or eye (mouth is less effective)
Bronchiolitis (lymphocytic peribronchiolar infiltration): endothelial sloughing, mucus secretion, airflow obstruction
pneumonia with mononuclear cell infiltration
acute complications: apnes, increased risk of infant aspiration
chronic complications: recurrent wheezing, bronchiectasis
pneumonia in immunocompromised
tx: ribavirin, bronchodilators, corticosteroids
prevention: infection control, IVIG for high risk infants
Respiratory Syncytial Virus
RSV
attaches via G protein, structure similar to RSV
infects all ages, most children are infected by age 5
infection mostly in winter
upper respiratory infection, bronchiolitis, pneumonia
co-infection with RSV and/or influenza possible
Metapneumovirus
MNV
Togaviridae family; rubivirus
enveloped, +ssRNA, icosahedral, only one major antigenic type
moderately contagious, incidence is highest in spring
pre-vaccination period: minor epidemic every 6-9 years, major every 30 years; most common in 5-9 years
post-vaccination period: increasing frequency in older children, cases in recent immigrants
transmitted by respiratory droplets
most infectious when rash develops but virus is shed before and after rash
infants with congenital infection may shed virus for months
no viral shedding after vaccination
many infections are asymptomatic
fever, maculopapular rash (face>body), LAD (posterior auricular, posterior cervical), mild sore throat, coryza, cough, mild arthralgia
arthritis is more common in adolescent/young adult women
Rubella
German Measles
most likely with viral infection of the pregnant woman in the 1st and 2nd trimesters
low birth weight, sensorineural deafness, blindness (congenital cataracts, glaucoma), congenital heart disease (patent ductus arteriosus), microcephaly, thrombocytopenic purpura, hepatomegaly, and severe cognitive impairment in the baby
preventable with maternal immunization
Dx: mild leukopenia with atypical lymphocytes, serology, PCR of amniotic fluid
Tx: supportive, Ig for susceptible pregnant woman after exposure
Congenital Rubella Syndrome
family Orthomyxoviridae
enveloped, negative ssRNA genome in 8 segments (genetic reassortment)
hemagglutinin and neuraminidase surface projections (subtype Type A)
virus enters respiratory tract via small particle aerosols (talking, coughing, sneezing)
infection limited to superficial cells of URT and LRT; penetrates columnar epithelial cell causing cell death; inhibits protein synthesis inducing apoptosis
loss of ciliated and mucus secreting epithelial cells reduces bacterial clearance
abrupt onset of illness
fever, rigors, myalgias, headache, sore throat, dry cough, nasal obstrucion
may progress to viral pneumonia
secondary bacterial infection possible
may be followed by Guillain-Barre (bilateral ascending paralysis)
Dx: nasopharyngeal swab, rapid antigen testing, PCR, viral isolation
inactivated vaccine: chick embryo culture, trivalent/quadrivalent
inactivated vaccine high dose: for 18 years
recombinant vaccine: insect cell culture, >18 years
live attenuated vaccine: nasal, 2-49 years
epidemic = seasonal outbreak of subtype that already circulate in the community
pandemic = global outbreak of new subtype that emerges in human population
wild water fowl are reservoirs, all human viruses arise from avian viruses
Influenza
highly pathogenic avian virus that spread form Asia to Europe and Africa
bird to human transmission with close contact, human to human transmission is rare
50% mortality, pandemic potential
cook poultry and eggs to internal temperature of 165 degrees
avian influenza
H5N1
Non-enveloped DNA viruses, over 50 serotypes
Infection may be lytic, latent (chronic), or lead to oncogenic transformation
Primary infection occurs early on during the first years of life
Upper and lower respiratory tract infections, eye infections, or lower urinary tract infections in children
transplated organs often affected
Respiratory infections are often asymptomatic but can cause mild pharyngitis or tracheitis; cough, fever, sore throat and rhinorrhea are common; in infants, pneumonia and bronchiolitis
Pharyngoconjuntival fever, epidemic keratoconjunctivitis, hemorrhagic cyctitis
infantile diarrhea with fever, intussusception, CNS infections (encephalitis, meningoencephalitis)
Dx: clinical, tissue culture, EM, Ab detection, ELISA, immunofluorescence
Tx: supportive in immunocompetent, antivirals in immunocompromised
Adenoviruses
important in transplant recipients, frequently involves transplanted organ
bilateral interstitial pneumonia, UTI, disseminated disease (lung, colon, CNS)
disseminated disease is more common in children and is associated with a high mortality rate
Adenovirus in immunocompromised host
clinical syndrome caused by Adenovirus
occurs in outbreaks
pharyngitis, conjuntivitis, rhinitis, cervical adenopathy, fever
associated with contaminated swimming pools and ponds
Pharyngoconjuntival Fever
clinical syndrome caused by Adenovirus
frequently bilateral, may last for 4 weeks
peri-auricular adenopathy
cornea involvement may last for months causing visual disturbances
contagious, spread to household contacts
Epidemic Keratoconjunctivitis
clinical syndrome caused by Adenovirus
more common in boys
hematuris, dysuria, urinary frequency
Hemorrhagic cystitis
small, non-enveloped DNA virus
only propagated in human erythroid progenitor cells
common in children by age 15
acquired via respiratory route
Children: erythema Infectiosum (Fifth Disease); self-limited syndrome with prodrome of fever, headache, nausea, and diarrhea followed by classic slapped cheek rash; second stage may follow with fain erythematous rash on trunk and limbs; manifestations are immune mediated
Adults: especially women; arthralgias or frank arthritis which is usually symmetrical and involves small joints; symptoms similar to acute rheumatoid arthritis
Underlying hematological disorders or iron deficiency anemia: transient aplastic crisis; dyspnea due to profound anemia, viremia
Underlying immunodeficiency: Pure red cell aplasia; chronic anemia, persistent viremia; lack or low parvovirus-specific antibody response
Dx: viremia detected with DNA hydribization in pure red cell aplastic crisis and transient aplastic hyperplasia; erythema infectiosum is not viremic, use ELISA; in immunocompromsed no Ab, use PCR
Tx: self-limiting, life-long immunity; in immunocompromised remove immunosuppression or give Ig
Parvovirus B19
small, spherical RNA viruses
Flaviviridae, Togaviridae, Bunyaviridae, Reoviridae
require a biting arthropod to complete the life cycle
must produce a level of viremia in vertebrate host for arthropod to become infected during blood meal
most are zoonoses, humans are incidental hosts (except Dengue)
Arboviruses
family Togaviridae
reservoir = primates
vector = mosquito (same species as Dengue)
Africa, Asia, Caribbean, South America, US
Biphasic illness
Initial presentation: 2-4 days incubation, resolves in 3 days
Fever, headache, back pain, myalgias, arthraglias, frank arthritis
Nonspecific maculopapular rash in 50%, facial edema
Chronic, debilitating polysrthralgias in a subset of patients: last for months to over a year
Affect peripheral joints, associated with teneosynovitis and Raynaud’s
Less common in children compared to adults
Death is rare but long recover results in morbidity and disability
Dx: PCR in early infection, IgM after 2 days of fever
Tx: no specific treatment
Chikungunya
family Flaviviridae
reservoir = macaques and humans
vector = mosquito
Urban – mostly transmitted by mosquitoes in peri-domestic environment (breed in standing water)
Four serotypes, all can cause fatal disease. Infection with one serotype confers life-long immunity to that serotype but only temporary (6 month) protection against heterologous serotypes
Asymptomatic 20-50% Undifferentiated fever (mild fever, usually in young children with first episode) Fever Syndrome Hemorrhagic Fever Shock Syndrome
warning signs of progression:
abdominal pain/tenderness, persistent vomiting, lethargy/restlessness, fluid accumulation, mucosal bleeding, sudden increase in hematocrit with rapid decrease in platelet count
transfer to ICU for fluid management and management of shock
Dx: clinical (tourniquet test, RT-PCR in acute phase, serology
Tx: supportive; in hemorrhagic fever and shock syndrome, fluid replacement is key (when signs of convalescence appear watch for overload)
Dengue
family Flaviviridae
reservoir = primates
vector = mosquito
endemic in sub-Saharan Africa and parts of South America
Biphasic illness, abrupt onset of illness 3-6 days after bite
Initial phase: extreme myalgias, headache, nausea, vomiting, conjunctival suffusion, Faget’s sign (relative bradycardia)
low WBC count, elevated liver enzymes
virus usually detectable in blood
3-4 days before resolution, followed by virus-specific IgG
Second phase: 15-20% recurrence after initial phase
Fever, hepatitis, jaundice, renal failure
Severe hemorrhage – hematemesis, melena, ecchymosis, bleeding from eyes, nose, bladder, rectum
25-50% mortality due to multisystem organ failure and shock
Life-long immunity in those who recover
Dx: IgM in initial phase, cross reactivity with other flaviviruses
Tx: supportive, no specific antiviral
Vaccination – live attenuated vaccine likely life-long immunity, required for travel to Africa and parts of South America
Yellow Fever
family Flaviviridae reservoir = birds vector = mosquito also transmitted via blood transfusion, and transplacentally infects humans and domestic animals
introduced to US in 1999 (migrating bird, illegal bird traffic, infected mosquito on airplane, infected traveler, or new viral strain)
most infections are asymptomatic
higher risk of disease in the elderly, immunocompromised, and with deletion in CCR5 gene which is protective against HIV
clinical manifestations: fever, neuroinvasive disease (meningitis, encephalitis, flaccid paralysis)
Dx: CSF IgM is more sensitive than PCR
Tx: supportive - fluids and respiratory support
West Nile Virus
family Flaviviridae
arboviruses that infect the CNS
reservoir = birds and small mammals
vector = mosquito
asymptomatic infection (children)
flu-like syndrome
encephalitis-meningitis syndrome (adults)
acute flaccid paralysis/myelitis
prognosis worsens with age, those who recover have residual weakness
Dx: CSF IgM is more sensitive than PCR
Tx: supportive, no specific antiviral
North American Encephalitis Arboviruses
St. Louis Encephalitis
clinical manifestation of West Nile Virus
Non-specific, influenza-like syndrome characterized by fever, headache fatigue, and myalgias
Neck pain and stiffness may be present but are not sue to meningitis – no elevated WBC on lumbar puncture
Rash in 25-50% - macropapular, present on trunk more than extremities
Usually recover within a week without permanent complication, fatigue may take longer to resolve
Rarely fatal although death due to cardiac arrhythmia or respiratory failure has been reported
West Nile Fever
clinical manifestation of West Nile Virus
Meningitis
West Nile Fever symptoms plus severe headache, neck stiffness, photophobia
20% cranial nerve palsies
Mildly elevated WBC, paradoxical increase in neutrophils
CSF protein may be slightly elevated but CSF glucose is normal
Patients usually recover without permanent neurologic complications
Encephalitis
Approximately half of WNND
More likely in elderly and immunocompromised
Severe encephalitis resulting in hospitalization and permanent neurologic damage (movement disorders, tremors, weakness)
Fatality rate is 20% and death is often due to cardiac arrhythmias or respiratory failure
Flaccid paralysis
Least common manifestation, mimics poliomyelitis
Weakness is usually unilateral but can involve more than one limb
Half of cases also present with encephalitis
Permanent neurological damage is common
Prolonged period of recovery
West Nile Neuroinvasive Disease
clinical manifestation of Dengue
Mainly in older children and adults
High fever plus two or more of the following: severe headache, retro-orbital pain, myalgias, arthralgias, diffuse erythematous maculopapular rash, mild hemorrhagic manifestations (petechiae, easy bruising, positive tourniquet sign
Plasma leakage from blood vessels and severe hemorrhage are usually absent
Patients usually recover without sequelae
Dengue Fever Syndrome
clinical manifestation of Dengue
Dengue fever symptoms
hemorrhagic manifestations: petechiae, purpura, ecchymoses, gingival bleeding, nasal bleeding, GI bleeding, increased menstrual flow
thrombocytopenia
plasma leakage: hemoconcentration, pleural effusion, ascites, hypoproteinemia
mortality >20% if not recognized
development is due to pre-existing heterologous antibodies
Dengue Hemorrhagic Fever
clinical manifestation of Dengue
Dengue Hemorrhagic Fever symptoms
circulatory failure: low BP, cold, clammy skin, narrow pulse pressure, hypoperfusion of organs
mortality >20% if not recognized
development is due to pre-existing heterologous antibodies
Dengue Shock Syndrome
Emerging Coronavirus: enveloped, ssRNA virus
First case: China 2002; spread to 37 countries on 5 continents
Short lived epidemic, no new cases since 2003
Likely developed from horseshoe bat coronavirus, detected in a type of cat (civit) eaten in China
Virus binds angiotensin converting enzyme II on the surface of human cells
Transmission by respiratory droplet or fomites
Secondary transmission to healthcare workers was common and required quarantine
Early in infection (after 5 day incubation): fever, myalgias, chills, dry cough
CXR shows infiltrates in 60%
Recover or enter late stage infection
Late stage infection: persistent fever, worsening pneumonia, watery diarrhea
25% require ICU, intubation, assisted ventilation
Overall mortality 10% with worse outcomes in the elderly and those with comorbid conditions
Dx: Difficult to distinguish clinically from other viral pneumonias
RT-PCR on lower respiratory tract samples or stool
Tx: supportive, no specific antiviral
infection control is essential
Severe Acute Respiratory Syndrome (SARS)
Emerging Coronavirus: enveloped, ssRNA virus
First case: Saudi Arabia 2012; spread throughout Arabian Peninsula, outbreak in S. Korea
Secondary transmission in healthcare workers
Source of virus remains, unclear but it may have come from camels or bats
Atypical pneumonia – fever, cough, dyspnea
GI symptoms; respiratory disease in those with comorbidities
45% mortality
Dx: RT-PCR to detect virus in nasopharyngeal aspirates, blood, feces
Tx: supportive
Middle East Respiratory Syndrome Coronavirus Infection (MERS-CoV)
Emerging Filovirus; RNA virus
First described in 1976, outbreaks of hemorrhagic fever in Sudan and DRC
Zaire strain: Gabon, DRC, Congo-Brazzaville
Sudan strain: Sudan and Uganda
Suspected reservoir is the fruit bat
Transmission through direct contact with body fluids, entry through mucosal surfaces and breaks in the skin
Infectious at onset of fever, through late stages or immediate post-mortem period
Incubation 2-21 days, abrupt onset of fever, chills, malaise, and myalgias
Progresses to prostration, rash (maculopapular, desquamates in survivors), nausea/vomiting/diarrhea/abdominal pain, cough/SOB/chest pain, postural hypotension/edema, headache/confusion/coma
Hemorrhagic manifestations in
Ebola Virus
Deltaretrovirus
infects T cells, endothelial cells, and fibroblasts
transmitted via cell associated virus - IVDU, contaminated blood products, sexual contact (more likely in women), breast milk
endemic in Japan and the Caribbean
associated with cellular transformation and oncogenesis
T cell lymphoma and myelopathy (tropical spastic paraparesis)
Human T Lymphocyte Virus 1
HTLV1
virus family
large, enveloped dsDNA viruses
outer envelop, tegument, icosapentahedral nucleocapsid, internal core
viruses indistinguishable on EM, most do not exhibit homology
Herpesviridae
HSV1, HSV2, VZV
site of latency = neuron
alpha herpesviruses
CMV, HHV6, HHV7
site of latency = monocyte, lymphocyte
beta herpesviruses
EBV, HHV8
site of latency = B lymphocytes
gamma herpesviruses
fever, anorexia, malaise, headache, tender regional LAD, vesicular rash on genitalia
may have aseptic meningitis
inflammation of the sacral nerve may lead to urinary retention which is more commonly seen in females
lesions may take several weeks to heal and may be more severe in an immunocompromised host
HSV primary genital infection
gingivostomatisis
generally seen in children
HSV primary oral infection
no concurrent anti-HSV antibodies to HSV1 or HSV2
primary HSV
evidence of prior exposure to the alternate type
HSV1 infection with HSV2 antibodies
HSV2 infection with HSV1 antibodies
non-primary HSV
infection with the same type as seen in serum antibodies
recurrent HSV
beginning of an HSV infection that does not fully develop due to preemptive or prophylactic treatment
Aborted lesions
occurs more often with HSV2 infection
induced by stress, sunlight, local trauma, menstruation, fever
prodromal symptoms: pain, burnign, tingling, itching
stereotypes lesions
lesions are fewer in number, less severs with fewer systemic symptoms and more rapid healing
HSV recurrence
most common with HSV1, except in infants (HSV2)
corneal scarring, frequent lid involvement, dendritic appearance
treated with topical antivirals
HSV Ketatitis/Conjunctivitis
HSV infection with involvement of the nail bed , may resemble bacterial infection
HSV1 in medical personnel, HSV2 in the general population
fever, pain, axillary LAD, vesicular lesion at the nail margin
heals in 2-3 weeks but may be recurrent
Herpetic Whitlow
more commonly seen with HSV2, also seen with HSV1
transmission from infected mother to baby at birth, especially when mother has active lesions, C-section is indicated
may cause seizures, blindness, psychomotor retardation, spasticity, developmental delay, and death
Neonatal HSV
alpha-herpesvirus
childhood illness before vaccination
late winter/early spring, seen in temperate more than tropical climates
high household attack rate, person to person spread via respiratory route, may be transmitted days before rash
associated with some mortality, mostly in leukemic children and immunocompromised adults
fever, rash (begins on scalp or trunk and spreads to extremities)
superficial vesicles in different stages of development
“dew drop on a rose petal” appearance
vesicles on mucus membranes quickly become ulcers
diagnosis: clinical, Tzanck prep (multinucleated giant cells), tissue culture, direct immunofluorescence
complications: hepatitis, pneumonitis, encephalitis; super infection of cutaneous lesions (GAS, staph aureus), Reye’s syndrome (aspirin use), Guillan-Barre
Varicella-Zoster Virus
incidence increases with age or immunosuppression
VZV latency in dorsal root ganglia
reemergence in dermatomal distribution (unilateral involving 1-3 dermatomes), 50% thoracic
prodromal pain
may have associated meningitis, dissemination to lung, liver, brain, post herpetic neuralgia
Herpes Zoster
Shingles
gamma herpes virus
expression of specific viral proteins leads to cellular transformation
developing countries: childhood (early infection associated with Burkitt lymphoma)
developed countries: adolescence, early adulthood
intermittent virus excretion in oropharyngeal secretions in adults, especially immunocompromised
virus multiplies in pharyngeal lymphoid tissue and possibly oropharyngeal epithelial cells
dissemination throughout lymphoreticular system
causes tranformation of B cells, atypical CD8 T cells are seen
may be asymptomatic
infectious mononucleosis syndrome: sore throat, fever, tonsillar enlargement with exudate, palatal petechiae, cervical LAD, hepatomegaly, splenomegaly (caution - rutpure), rash to ampicillin
Diagnosis: atypical lymphocytosis, Thrombocytopenia, mild elevation of transaminase, monospot (heterophile Ab), specific virus Ab, PCR
complications: hemolytic anemia, thrombocytopenia, neurologic disease
no effective treatment, corticosteroids for hematologic and neurologic conditions
assoicated malignancies: Burkitt lymphoma, Hodgkin’s lymphoma, CNS lymphoma, lymphoproliferative syndromes, nasopharyngeal carcinoma
Epstein-Barr Virus
beta herpesvirus
largest human virus, increases size of infected cells, prevents HLA1 molecules from reaching cell surface
transmitted by contact with saliva, urine, semen, contaminated blood products, vertical (intrapartum, at delivery, breast milk), day care setting
immunocompetent host: asymptomatic, mononucleosis, congenital
immunocompromised host: retinitis, pneumonitis, colitis, esophagitis, encephalitis, myelitis
diagnosis: cytoplasmic and nucler inclusions (owl eye inclusions = aggregates of CMV nucleoprotein cores), serology, PCR, culture
Cytomegalovirus
primarily seen in HIV or transplant patients
necrotizing chorioretinitis (peripheral or central) irregular sheathing of blood vessels, development of white granular lesions with hemorrhage blurred vision, floaters
CMV retinitis
most likely to occur with primary infection during pregnancy and intrapartum transmission
severe clinical manifestations involving multiple organ systems
jaundice, hepatosplenomegaly, petechial rash, microcephaly, motor disability, chorioretinitis, cerebral calcifications
Congenital CMV
beta herpesvirus
infects multiple cell types (T cell, B cells, NK cells, epithelial cells, macrophages, glial cells
most people have been infected
more common in spring/fall, spread by contact with saliva
Roseola infantum, usually benign childhood illness
abrupt onset, high fever, suboccipital adenopathy, abrupt disappearance of fever and onset of macular rash
complications: usually self-limited and mild but can cause febrile seizures and rare encephalitis
mononucleosis-like illness in adults
diagnosis: serology
treatment is usually not indicated except in immunocompromised hosts
HHV6
gamma herpesvirus
attaches to heparan sulfate and targets endothelial or spindle cells which may result in Kaposi’s sarcoma or B cells which may result in lymphoma
Kaposi’s sarcoma: vascular tumors usually associated with HIV
Castleman’s disease: focal or multicentric lymphoma
transmission via sexual contact
HHV8
