Transcript virus-1 - Biomedic Generation

Course objectives
• To promote Islamic values through an
appreciation of the role of microbes in the
well-being of human life.
• To familiarise students with structurefunction relationship of microbe and
parasite in diseases.
• To acquire basic skills in the identification
and isolation of microbial pathogens.
Learning outcomes
• Demonstrate understanding of the principles of
diagnostic medical microbiology and the clinical
correlations.
• Make observations, understand the fundamental
elements of experimental design, generate and analyse
data on pathogenesis and control of disease.
• Demonstrate proficiency in collection, interpretation, and
presentation of scientific data in medical microbiology
when conducting a research.
• Communicate about case studies using appropriate oral
and written means.
Parvovirus and Herpes virus
SBM 2044
Medical Microbiology
Parvoviruses
• Are the simplest DNA
animal viruses – host
dependent for viral
replication.
• The only pathogenic
parvovirus to humans, B19
of genus Erythrovirus
– cause of erythema
infectiosum “slapped-cheek disease” or “fifth
disease”.
• Common in children age 5-15.
Structure & composition
• Icosahedral, non-enveloped.
• Virions are extremely resistant to
inactivation. Stable at pH3-pH9; 56°C for
1hr.
• Virions contain 2 coat proteins. The major
capsid protein , VP2, represents ~ 90% of
virion protein. The non-structural protein –
for virus replication and may modulate
host cell genes and cause diseases.
• Genome is ~5kb, linear, single-stranded
DNA.
• A negatively stained preparation of parvovirus as seen
by transmission electron microscopy. The individual
virions have a diameter of only 22nm. (nm=one-millionth
of a millimeter) www.wadsworth.org
Parvovirus replication
• Highly tropic for human erythroid cells. Cellular
receptor for B19 is blood group P antigen
(globoside) – expressed in mature erythrocytes,
erythroid progenitors, endothelial cells, placenta.
• Viral replication in nucleus.
• Major sites of viral replication are assumed to be
the adult marrow and fetal liver, causing cell
death by inhibiting RBC production.
• Both virus-specific IgM and IgG Abs are
produced following B19 infection.
Pathogenesis
• Transmission presumably via the resp
route.
• B19 can be found in blood and resp
secretions. Some may replicate in
intestinal mucosal cells and cause
enteritis.
Fifth disease
• Most common in school children.
• Symptoms: rash, pain in joints
(arthropathy) in adult cases which mimic
rheumatoid arthritis.
• Viraemia 1 week after infection, virus
present in nasal washes, gargle
specimens.
• Patients are treated symptomatically.
Herpesviruses
• Everyone will get
herpesviruses at
some time.
• Large viruses;
enveloped; all have a
core of ds DNA in the
form of a toroid,
surrounded by a
protein coat that
exhibits icosahedral
symmetry and 160
capsomeres.
Structure and composition
• Envelope is derived from nuclear membrane of
infected cell and contains viral glycoprotein
spikes.
• Genome is a linear ds DNA of 124-235kbp.
• Sequence arrangement – herpesvirus possess
terminal and internal repeated sequences.
• Large genome and encodes >100 proteins.
• Genomes of herpes viruses. HSV, VZV and CMV have inverted
repeat sequences. This results in the formation of more than one
isomer by recombination. Because VZV has only two inverted
repeats, it can only form two isomeric forms. Direct repeats do not
allow recombination and so EBV and HHV6 have only one isoform.
Common name
Sub- Clinical features
family
1 Herpes simplex virus-1
α
Gingivostomatitis, cold sores,
encephalitis
2 Herpes simplex virus-2
α
Genital herpes, meningo-encephalitis
3 Varicella-zoster virus
α
Varicella (chickenpox), zoster
(shingles)
4 Epstein-Barr virus
γ
Mononucleosis (glandular fever),
Burkitt’s Lymphoma, nasopharyngeal
carcinoma
5 Cytomegalovirus
β
Mononucleosis, congenital CMV
disease, hepatitis, retinitis in the
immunocompromised
6 Human herpes virus-6
β
7 Human herpes virus-7
β
Exanthum subitum/Roseola infantum,
febrile childhood illness
8 Kaposi’s sarcomaassociated
γ
Herpes Simplex Viruses
• HSV-1 and HSV-2 exhibit substantial
sequence homology. They differ in their
mode of transmission: HSV-1 by contact
(saliva), whereas HSV-2 is transmitted
sexually or from a maternal genital
infection to a newborn.
• HSV have rapid growth cycle, 8-16hr.
• Large genome 150kbp which encodes >70
polypeptides.
HSV: Pathogenesis
• 1) Primary infection:
• HSV-1 infections are usually limited oropharynx;
HSV-2 is usually transmitted by genital routes.
Viral replication occurs at the site of infection.
• Virus then invades local nerve endings and is
transported to dorsal root ganglia.
• 2) Latent infection:
• HSV-1 infects the trigeminal ganglia, whereas
HSV-2 in sacral ganglia. Both in non-replicating
states.
HSV: Pathogenesis
• 3) Reactivation:
• Provocative stimuli (fever,
stress, pneumococcal
infection) can trigger
recurrence – many
asymptomatic.
Symptomatic recurrences
are usually manifested as
cold sores near the lip.
http://www.sumanasinc.com/webcontent/anisamples/microbiology/herpessimplex.html
•
•
Expression of herpesviruses genes.
http://pathmicro.med.sc.edu/
HSV: Immunity
• Newborns acquire passively transferred
maternal Abs up to 6-month old.
• 6-month to 2 years : highly susceptible
• HSV-1 Abs begin to develop in early childhood.
• HSV-2 Abs rise during the age of adolescence.
• During primary infection, IgM followed by IgG
and IgA for long periods. NK cells and
interferons are important in controlling both
primary and recurrent HSV infections.
• After recovery, the virus is carried in a latent
state in the presence of Abs.
HSV- Diagnosis
• Cytopathology: to stain scrapings from the base
of lesions (of mucous membranes of the
mouth/genitalia) and look for multinucleated
giant cells and intranuclear eosinophilic
inclusions bodies.
• Tissue specimen or fluid is introduced into a
primary cell line such human embryonic kidney
TC and is then observed for cytopathic effects
within 24-48h – essential for
immunocompromised and neonatal patients.
• Serological analysis is useful for primary
infection but not recurrence, because the Ab titre
usually does not increase.
Varicella-Zoster Virus
• Varicella (chickenpox) is a mild, highly
contagious disease mainly in children,
characterized clinically by a generalized
vesicular eruption of the skin and mucous
membranes.
• Zoster (shingles) is characterised by a rash
limited in distribution to the skin innervated by a
single sensory ganglion.
• Varicella is the acute disease, from primary
contact with the virus, whereas zooster is the
response of partially immune host to reactivation
of varicella virus present in latent form in
neurons in sensory ganglia.
VZV - Pathogenesis
• Varicella:
• Route of infection is the mucosa of the Upper
Resp T or the conjunctiva.
• Replication in regional lymph nodes → 1°
viraemia which leads to replication in liver and
spleen.
• 2° viraemia involving infected mono-nuclear
cells transports virus to the skin → rash.
• Swelling of epith cells, ballooning degeneration
and accumulation of tissue fluids.
• Host humoral and cellular immune responses
are important immune defence.
VZV- Pathogenesis
• Zoster:
• Similar skin lesions to those of varicella.
• Often only a single ganglion may be
involved. Distribution of lesions
corresponds closely to the areas of
innervation from an individual dorsal root
ganglion.
• Cell-mediated immunity is probably the
most important host defense.
VZV- Clinical findings
• Incubation period is 10-21 days.
• Malaise and fever are the earliest symptoms, followed by
rash (first on trunk and then on the face, the limbs and
buccal and pharyngeal mucosa in the mouth).
• Rash lasts for 5 days.
• Complications are rare in children. Eg. Encephalitis,
varicella pneumonia.
• Zoster – usually occurs in immunocompromised. Starts
with severe pain in the area of skin supplied by one or
more groups of sensory nerves and ganglia.
• Trunk, head and neck are commonly affected.
• Immunity: Abs induced by varicella vaccine can persist
for at least 20 years.
Cytomegaloviruses
• The name derives from the massive
enlargement of CMV-infected cells.
• DNA genome 240kbp (largest of HHV)only a few proteins encoded by the virus
(>200) have been characterised.
• CMV are very species-specific and cellspecific – all attempts to infect animals
with human CMV have failed. CMV
replicates only in human fibroblasts and
replicates very slowly in cultured cells.
CMV - Pathogenesis
• A) Normal hosts:
• CMV is transmitted by close contact from
person-to-person.
• 4 to 8 weeks of incubation period.
• Virus causes systemic infection and is an
infectious mononucleosis-like syndrome.
• Lifelong latent infections, like all herpesviruses.
• Cell-mediated immunity is depressed with
primary infections and may take months to
recover.
CMV - Pathogenesis
• B) Immunocompromised hosts:
• Immunocompromised such as those receiving
organ transplants, on chemotherapy, AIDS are at
greatest risk.
• Severe infection and pneumonia is the most
common complication.
• C) Congenital and perinatal infections:
• Virus can be transmitted in uterus with both
primary and reactivated maternal infections.
• Babies suffer with cytomegalic inclusion disease
and will exhibit developmental defects and
mental retardation.
Epstein-Barr virus
• The major target cell for EBV is the B
lymphocytes, and infected B lymphocytes are
immortalised by the virus.
• Discovered in African children with unusual
malignant tumour (Burkitt lymphoma).
• The epithelium of oropharynx is the portal entry
for EBV during 1° infection. Virus then moves to
parotid gland, to replicate and undergoes
latency state.
• Infectious mononucleosis are presented with
sore throat, hig fever, cervical lymphadenopathy
– which develop after 30-50 days.
Burkitt Lymphoma
Human Herpesvirus 6
• HHV-6 appears to be unrelated
antigenically to the other known human
herpesviruses.
• Virus grows well in CD4 T lymphocytes.
• HHV-6 infections usually occur in early
infancy, causing roseola infantum
characterised by high fever and skin rash.
• Mode of transmission is possibly via oral
secretions.
Human Herpesvirus 7
• A T-lymphotropic human herpesvirus.
• Immunologically distinct from HHV-6.
Human Herpesvirus 8
• Also called Kaposi’s sarcoma-associated
herpesvirus (KSHV).
• Virus can be transmitted through organ
transplants.
• KSHV is the cause of Kaposi’s sarcomas,
vascular tumours of mixed cellular
composition.
Treatment
•
•
•
•
Acyclovir for HSV and VZV.
Gancilovir for CMV
Famcyclovir for VZV
Varicella-zoster immunoglobulin is used to
prevent disease when eg. Immunocompromised are exposed to infection.