and Antimicrobials for viruses)
Table of contents :
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Generalities for viroses
Web resources |
,
acute
bronchitis
or interstitial
pneumonia
,
acute
bronchitis
or interstitial
pneumonia
("recruit fever")
or interstitial
pneumonia
("recruit fever"),
acute
bronchitis
or interstitial
pneumonia
("recruit fever")
in babies
with dissemination or urinary
tract infections (UTI)
in immunocompromised hosts
with dissemination or urinary
tract infections (UTI)
in immunocompromised hosts
formation hence affecting presentation of the immunoproteasome-dependent
epitope E1B. E1A interacts with the 19S S4
ATPase subunit of the 26S
proteasome.
with dissemination or urinary
tract infections (UTI)
in immunocompromised hosts
or Bordetella parapertussis,
although evidence of other infectious agents, such as adenoviruses types
1, 2, 3, 5, and 6, can be demonstrated
(RR = 5-6)
with dissemination or urinary
tract infections (UTI)
in immunocompromised hosts
,
acute
bronchitis
or interstitial
pneumonia
("recruit fever")
after 24-72 hours incubation => cholangiohepatitis
occurs in immunocompromised hosts as a result of ascending infection from
the gastrointestinal tract to the biliary tree.
as receptor).).
Respiratory infections in children are short-lived and rarely life-threatening.
Outbreaks of adenovirus respiratory infections have been common among military
recruits (mainly types 4, 7, 14 and 21), where rates of hospitalisation
have reached 20%. As a result vaccines were developed against adenovirus
types 3, 4, 7 and 21, but later withdrawn. Most outbreaks of pharyngoconjunctivital
fever in school-age children have occurred occur during the summer, whereas
the outbreaks among military recruits have occurred during winter, probably
reflecting a different mode of transmission. Adenovirus types 8, 9 and
11 have been associated with outbreaks of keratoconjunctivitis (also known
as shipyard eye) in adults. However, whereas multiple serotypes from different
species have been described as causing cases or limited, irregular outbreaks
of ocular disease in humans, there are only a few serotypes that regularly
cause larger outbreaks or epidemics. The 2 types of ocular disease that
are commonly caused by adenoviruses are pharyngoconjunctival
fever (PCF)
and epidemic
keratoconjunctivitis (EKC).
An interesting observation is that the 3 serotypes that cause EKC (Ad8,
Ad19, and Ad37) use a cellular receptor (sialic acid) that is different
from the cellular receptors used by other adenoviruses (CAR or CD46)
.)
out of 27 in a wildlife shelter in Nantou County were put down after they
were diagnosed as carriers
,
and death
: the BTLA binding site on HVEM overlaps with the binding site for the
gD, but is distinct from where LIGHT binds, yet glycoprotein D inhibits
the binding of both ligands, potentially nullifying the pathwayref.
Coreceptors : herpesvirus
entry protein B (HveB) / poliovirus receptor-related 2 (PVRL2) / CD112
/ CD155 and herpesvirus
entry protein C (HveC) / poliovirus receptor-related 1 (PVRL1) / nectin-1
/ herpesvirus Ig-like receptor (HIgR) (that confined with E-cadherin
to adherens junctions in epithelial cells is not very accessible to virus,
whereas dissociation of cell junctions releases nectin-1 to serve more
efficiently as an entry receptor)
of viral infection. HSV-1 reduces CD1d
surface expression on APCs. HSV-1 did not inhibit CD1d protein synthesis
or enhance constitutive CD1d endocytosis. Instead, HSV-1 prevented the
reappearance of endocytosed CD1d on the cell surface by redistributing
endocytosed CD1d to the lysosome limiting membrane. HSV-1 might also inhibit
the transport of newly synthesized CD1d to the cell surface. Such inhibition
of CD1d surface expression impaired APC–mediated stimulation of NKT cells,
supporting the idea that this mechanism may be an important HSV-1 immune
evasion strategyref.
and oropharyngitis
in babies before age 3 (the most common kind of primary infection) => eschar
(=> squamous lip carcinoma),
self-limiting within 10-14 days.
and sometimes chills occur.
that erode and spread. The lower lip is more commonly affected than the
upper lip.)
in individuals who have active or quiescent atopic
dermatitis (AD).
on the finger or hand due to bacterial superinfection, often seen in health
cares workers (dentists, ..) who have a tendency to touch HSV lesions without
dressing gloves)
in adults => epilepsy
(?)
(type II hypersensitivity mediated by Th1
effector cells) leading to scarring, opacity, and blindness, and it is
an important problem in common corneal surgeries or acute monolateral
follicular conjunctivitis.
In the preclinical phase, when HSV-1 replicates in the corneal epithelium,
neutrophils invade the underlying corneal stroma. This transient response,
triggered by replicating virus, is thought to control HSV replication and
limit viral spread into peripheral tissues. During the clinical phase,
a second wave of inflammatory cells, predominantly consisting of neutrophils,
infiltrates the corneal stroma and destroy it. Paradoxically, virus antigens
are largely focused in the epithelial layer of the cornea and not in the
stromal layer, and viral antigens are eliminated before stromal inflammation
develops. It is not clear what drives inflammation, whether viral antigens
are necessary, or how viral antigens reach the stroma. It has been proposed
that HSV travels from the corneal epithelium to sensory ganglia then returns
to the stroma to cause disease. However, there is also evidence of HSV
DNA and infectious virus persistent in corneas, and HSV can be transmitted
to transplant recipients. US9- HSV mutant, that had diminished
capacity to move in neuronal axons, replicated and spread normally in the
mouse corneal epithelium and to the trigeminal ganglia. However, US9-
HSV
was unable to return from ganglia to the cornea and failed to cause periocular
skin disease, which requires zosteriform spread from neurons. Nevertheless,
US9- HSV caused keratitis. Therefore, herpes keratitis can occur without
anterograde transport from ganglia to the cornea, probably mediated by
virus persistent in the cornearef.,
interstitial
pneumonia
: lethality 50%)
=> vesicles
(?)
(?)
(Lipschutz inclusions), owl-eye
inclusions
is more susceptible to HSV-1 encephalitis than Aotus
trivirgatus
(expensive, difficult to obtain and to maintain in captivity)
.
;
alcoholic povidone-iodineref.
Coreceptors : herpesvirus
entry protein B (HveB) / poliovirus receptor-related 2 (PVRL2) / CD112
/ CD155 and herpesvirus
entry protein C (HveC) / poliovirus receptor-related 1 (PVRL1) / nectin-1
/ herpesvirus Ig-like receptor (HIgR)
,
vulvovaginitis,
balanoposthitis,
non-gonococcal
urethritis (NGUs),
proctitis
(severe in male homosexuals). The lesions are very superficial (unlike
chancroid or syphilis, whose lesions are lumpy). The primary lesions stay
for 2-3 weeks, but recurrent usually heal within 3-5 days.,
and visceral disease (interstitial
pneumonia,
hepatic necrosis). If the mother has been seropositive for some time before
the birth, then transplacental IgG serve as a protective mechanism for
the newborn. >50% mortality.,
seborrhoic
dermatitis,pemphigus
or Wiskott-Aldrich
syndrome
=> generalized herpes (including erythema
multiforme,
herpetic
stromal keratitis (HSK),
retinal necrosis)
when the virus travels up the nerve to the brain instead of down towards
the lip (lethality 50%)
: recurrent aseptic meningitis characterized by headache,
malaise, meningeal sings, and monocytes in the CSF.
and acute pharyngitis
in adults following oro-genital contacts => eschar
(=> squamous lip carcinoma)
(priming effect for HPV-6, HPV-10,
HPV-11,
HPV-16,
and HPV-18 ?),Cowdry
type A inclusion bodies
(Lipschutz inclusions).
.
)
or cidofovir
(if resistance occurs => foscarnet),
idoxuridine,
vidarabine
and trifluridine.
=> vesicles
(Sklowsky's symptom : when light pressure with the index finger
is made upon the healthy skin near, and then over, a vesicle in varicella,
the wall of the vesicle easily collapses and the contents are discharged)
=> pustules
with "starry sky" look (contemporaneous presence of papulae, vesicles
and scubs on whole body). + salicylates (+ Influenzavirus
A H3N2 ?) => Reye's
syndrome
. Sequelae : vesicles,
impetigo,
neuraxitis,
acute
glomerulonephritis,
acute
hepatitis,
keratitis,
interstitial
pneumonia
(1%, expecially in immunocompromised adults => death due to respiratory
failure), postvaricella
purpura fulminans
(due to autoimmune thrombocytopenia
and DIC),
lupus anticoagulant (LAC), cerebellitis
(=> ataxia), post-infective encephalitis
(PIE : 1 case out of 4,000-10,000), overinfection by Streptococcus
pyogenes
(expecially necrotizing fasciitis and TSLS) => thrombosis. Lifelong presence
of neutralizing antibodies prevents reinfection. Virus undergoes latency
in satellite cells of a sensitive ganglion.
month 4 => eye, brain and limbs injuries in newborn
and iridocyclitis)
if reactivation occurs in geniculate ganglion of facial nerve
if reactivation occurs in uditive nerve
recipients, visceral disease may precede or occur in the absence of the
characteristic signs on the skinref1,
ref2,
ref3,
ref4.
In such cases, in which patients present with severe unexplained abdominal
pain, diagnosis and treatment are usually delayed until signs of the infection
appear on the skin or, in the absence of a rash, the diagnosis is made
at necropsy. In allogeneic BMT recipients, the symptoms may be misdiagnosed
as graft-versus-host disease, and immunosuppressive treatment instituted,
with potentially grave consequencesref.
In view of the significant morbidity and mortality, early diagnosis of
visceral involvement of herpes zoster is highly desirable. A case series
of 4 patients with visceral herpes zoster was reported in whom large concentrations
of DNA from VZV were detectable in blood by PCRref
before signs of infection appeared on the skin, thus enabling early diagnosis
and treatmentref,
encephalitis
: VZV DNA was detected more frequently (P < 0.05) in the CSF of MS group
(31.6%), particularly among the relapsing-remitting MS patients (43.5%),
compared with patients with other neurological diseases (10.7%)ref
,
Cowdry
type A inclusion bodies,
balloon-like CPE
protects from primary infection but not from reactivations; the only way
to prevent shingles is eradication via massive antiviral drugs (vidarabine,
acyclovir)
while having chickenpox, before the virus shelters into ganglia (where
drugs can't reach it).
(prodrug : valacyclovir) or famciclovir
in a carrier state for long periods of time and then be reactivated. Once
introduced into a herd the virus usually remains there and it can continually
affect reproductive performance at varying levels. The virus can survive
for up to 3 weeks outside the pig. The virus crosses the uterus and placenta
and infects the foetuses.
,
nervous signs, reproductive failure, abortions, mummified piglets, stillbirths,
birth weak litters. Swine generally appear asymptomatic, and the 1st noticed
signs may be abortion, or a high mortality in piglets. Mortality in pigs
under a month old may be close to 100%, but only about 10% in pigs as old
as 6 months. Other clinical signs include fever, depression, coughing,
sneezing, constipation, seizures, ataxia, and circling. Excess salivation
may be noticed in both piglets and mature pigs.,
Felis
catus,
... : nervous signs, death. Infected cattle and sheep show signs of pseudorabies
by scratching and biting themselves. Pseudorabies in dogs and cats may
manifest itself as sudden death. In cattle, signs include intense itching
followed by neurological signs and death. In dogs, signs are evidenced
by intense itching,,
sneezing, coughing, interstitial
pneumonia.
Nervous signs including incoordination, fits, Aujeszky's itch / mad
itch, and meningitis.
Some strains of the virus can cause severe respiratory disease and others
severe acute
rhinitis.
Usually low mortality. However, the pathogenicity to human is controversial
: maybe it is dangerous only for immunocompromised hosts.
: B preferentially binds EGFR and EGFR-ErbB3 oligomeric moleculesref.
HCMV infection results in a rapid decrease in EGFR expression, which implies
that the interaction between HCMV and EGFR occurs at an early stage of
virus and host contactref
on monocytes (and DCs) and neutrophils (leukotropism)
and inhibits NK cell cytotoxicityref
and MICB,
retaining them in the cell and effectively masking NK-cell recognition.
gp40,
the ortholog murine cytomegalovirus (MCMV) protein, disrupts the RAE-1-NKG2D
interaction in mice by sequestering RAE-1 molecules, but not H60.
ortholog. that induces retention of MHC class II+ vesicles in
an abnormal perinuclear distribution in DCs.,
modulating the host antiviral response even before the newly infecting
viral genome becomes transcriptionally activeref.
products, resulting in the rapid degradation of HLA-DRa
and HLA-DMa in DCs.
complexes in the ER.
products to Derlin-1, a human homologue of yeast Der1p, a protein essential
for the degradation of a subset of misfolded ER proteins catalysed by US11,
but not by US2ref.
Derlin-1 interacts with US11, a virally encoded ER protein that specifically
targets MHC class I heavy chains for export from the ER, as well as with
VIMP, a novel membrane protein that recruits the cytosolic p97 ATPase and
its cofactorref.
US11 transports MHC class I H chains back into the
cytosol, where they are deglycosylated by host N-glycanase and then
degraded by the 26S
proteasome|
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| 18÷29 |
47.4 %
|
93.3 %
|
35.7 %
|
| > 30 |
62.5 %
|
93.8 %
|
45.3 %
|
| every age |
54.3 %
|
93.5 %
|
42.7 %
|
(?).
with no
pharyngotonsillitis
and Downey type I atypical lymphocytes => immunodeficiency,
cold
agglutinin disease.
Samples for direct diagnosis vary with time : oropharyngeal swab => blood
=> urine. Virus undergoes latency in PBMCs.
(24% higher likelihood than unaffected ones)
or syndrome : cytomegalovirus mononucleosis occurring about 3 to 6
weeks after extracorporeal circulation or multiple blood transfusions in
open heart or other surgical procedures
(Guillain-Barré
syndrome)
and cytomegalovirus chorioretinitis
("pizza pie" look) fist monolateral, then bilateral
:
: CMV seromismatched patients (donor+/recipient-
or D+/R-) have a 60-80% probability of primary CMV
disease and a significantly higher rate of acute rejection than non-seromismatched
patients (72% vs. 54.2%, P=0.005). Using multiple logistic regression,
CMV seromismatch, delayed graft function, and biological induction were
identified as independent predictors of acute rejection. The adjusted odds
ratios for these are 2.28, 1.65, and 0.52, respectively. In such cases
chemoprophylaxis is justified, at least in those patients who are are found
to have 1 or more pp65+ cells per 150,000 peripheral WBCs examined
(preemptive therapy)
: the greater the viral load, the higher the risk of vascular lesion
rejection
chronic rejection
chronic rejection
,
owl-eye
inclusions
is not effective due to lack of tk
oral chemotherapy (5 mg / kg IV or 1000 mg q8h PO) has been shown in
SYNTEX 1654 trial (patients affected by both HIV-1
and CMV). Alternatively 5 mg/kg i.v. twice daily with adjustment for renal
function : if resistance occurs (demonstrated by plaque reduction assay
or quantitative CMV-DNA hybrid capture assay showing deletions in the UL97
codon range 591-607) =>
(resistance conferred by mutation in the DNA polymerase gene at codon 756
(E-D substitution). However, foscarnet resistance mutations that have been
confirmed by marker transfer do not confer crossresistance to cidofovirref1,
ref2.3,
18 )
alone (induction dose 200 mg/day for 7 days, followed by a maintenance
dose of 50 mg/day, targeting a serum level of 60-80 mg/ml
of the active metabolite A77 1726)ref1,
ref2,
ref3,
ref4,
ref5,
ref6,
ref7,
ref8
or in addition to foscarnetref1,
ref2
or ganciclovirref.
Leflunomide is a new disease-modifying antirheumatic drug approved in 1998
in the United States for the treatment of rheumatoid arthritisref.
Among its proposed mechanisms of action are inhibition of T- and B-cell
proliferation by interference with the de novo pathway of pyrimidine synthesis
via inhibition of the enzyme dihydroorotate dehydrogenase and inhibition
of phosphorylation of specific tyrosine kinases involved in T- and B-cell
activityref.
Leflunomide is increasingly recognized as a potent immunosuppressive agent
for the prevention and treatment of rejection in solid organ transplant
recipientsref.
It has also been reported to have novel anti-CMV activity in vitro,
utilizing a mechanism different from that of other antiviral agentsref1,
ref2.
The mechanism of leflunomide antiviral activity is a topic of active research,
but it does not appear to affect transcription of immediate-early or late
viral genes or to inhibit viral DNA polymerase activity. It appears to
inhibit virion assembly at a late stage by preventing viral nucleocapsids
from acquiring their tegumentref.
As leflunomide does not affect DNA polymerase or other aspects of DNA replication
of CMV, it would be expected not to show crossresistance with other agents.
One previous anecdotal report suggested a response to leflunomide and cidofovir
in a transplant patient with CMV resistant to ganciclovir and foscarnet.
Leflunomide also appears to have antiviral activity against HSV as wellref.
Renal compromise may alter the efficacious blood level targetref
and patients with elevated serum creatinine may have substantially reduced
protein binding; thus the effective (and toxic) level might be reduced.
This has been cited as an explanation for significant variation in active
metabolite pharmacokinetic features in a series of patients with chronic
renal allograft dysfunction treated with leflunomideref.
Treatment of pregnant women with primary CMV infection with CMV-specific
monthly hyperimmune globulin (100 U/kg i.v.). is safe, and the findings
of this nonrandomized study suggest that it may be effective in the treatment
and prevention of congenital CMV infection. A controlled trial of this
agent may now be appropriateref1,
ref2
