Measles, Rubella, Varicella Flashcards
Members of the Paramyxovirus family of viruses - features
negative sense
single-stranded RNA virus
Large, helical
Enveloped
Parainfluenza virus is part of Paramyxovirus and orthomyxovirus is inflluenza (T/F)
True
Paramyxovirus is segmented and influenza is non segmented (T/F)
False; Paramyxovirus is non segmented and influenza is segmented
The family is divided into 3 genera
- Parainfluenzavirus
- Pneumovirus
- Morbillivirus
Pneumonia, bronchitis and croup, especially in children, and Mumps - under which genera of Paramyxovirus?
Parainfluenzavirus
Measles; Canine Distemper Virus - which genera of Paramyxovirus?
Morbillivirus
Respiratory Syncytial Virus (RSV), causes pneumonia - which genera of Paramyxovirus?
Pneumovirus
Is replication basically the same for all viruses in paramyxovirus group?
Very similar for all viruses in this group.
What is the diff in replication for viruses in paramyoxvirus group compared with influenza in same group?
All the action occurs in the cytoplasm for the other viruses
Unlike influenza, Paramyxovirus replication is resistant
to ________ _
Actinomycin D
Nucleocapsid - define
Viral genome encapsulated by the nucleocapsid protein; it is generally inside the cytoplasm.
Syncytium - define
a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei.
What occurs due to the syncytium formation in Measles Virus (MV)?
What are the MV cells referred to as?
A large excess of nucleocapsids are produced in infected cells, which form characteristic cytoplasmic inclusion bodies
Warthin Finkeldey cells
Measles virus (MV), a paramyxovirus, has two glycoproteins which are?
haemagglutinin (HA) and fusion (F) protein
Role of MV glycoproteins
responsible for virus attachment and entry
During MV infection, both the viral _________ are
synthesized in the ________ _________ and are
_______ to the cell surface where they cause _____ with the neighbouring cells
During MV infection, both the viral glycoproteins are
synthesized in the endoplasmic reticulum and are
transported to the cell surface where they cause fusion
(syncytium formation) with the neighbouring cells
Syncytium is rare in MV (T/F)
False; Syncytium is very common
Name one of the most infectious diseases known
Measles
Before ____ almost everyone contracted measles
1963
Known hosts for MV
Humans, monkeys, rodents
MV is the single leading cause of _______ _________
death among children in _____ - more than
AIDS, tuberculosis, and malnutrition
MV is the single leading cause of vaccine-preventable
death among children in Africa - more than
AIDS, tuberculosis, and malnutrition
Neuraminidase spikes absent in MV morphology (T/F)
True
Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins, thereby freeing the virus to infect other cells in the host organism.
Pleomorphic – define
A term used in histology and cytopathology to describe variability in the size, shape and staining of cells and/or their nuclei.
MV - structural features
- pleomorphic spherical structures
- 100-250nm diameter
- Inner nucleocapsid contains coiled helix of ssRNA and three proteins
- Outer envelope contains three other proteins
Terminus
One end of a protein molecule
Capsid structure involving helical core and N terminus
Capsid has an interior helical core around which the RNA is wound
N-terminus domain of the capsid protein forms an exterior helical covering that protects the viral genome.
– Researchers wishing to design antiviral drugs may want to disrupt the assembly of this helical capsid
Function of N protein in MV
The N protein encapsidates (surrounds) genomic RNA to shield RNA from nucleases and RNA-mediated silencing
– a function reflected in its ability to self-assemble into nucleocapsid particles in the absence of other viral proteins
RNA synthesis by nonsegmented negative-stranded RNA viruses (nsNSVs) is carried out by an interplay between at least four components which are?
the genomic RNA,
the nucleoprotein (N),
the phosphoprotein (P),
and the polymerase or large protein (L).
Viral polymerase complex made of the polymerase L associated with its cofactor P performs what function in MV?
Transcription and replication
Cofactor, P protein, plays a central role in nsNSV RNA synthesis (transcription)- how?
It binds to and stabilizes both L and N in an RNA-free form;
It tethers the polymerase onto the nucleocapsid, thus giving access to the shielded RNA template;
It regulates RNA synthesis
F protein function in MV
F proteins expressed at the plasma membrane of infected cells could mediate fusion with adjacent cells to form syncytia (a cytopathic effect that could lead to tissue necrosis)
H protein function in MV
Attaches the virus to cell receptors and thereby initiating infection.
Binding of H protein to the receptor induces a conformational change that allows the F protein to trigger virion/cell membranes fusion.
M protein function in MV
2D array associated with the membrane.
Virus development
– Incorporation of the surface glycoproteins and the RNP (ribonucleic complex) at sites of virus assembly.
Measles Virus environmental stability
- Can live up to two hours on surfaces
- 30 minutes in aerosol form
- Heat sensitive
- Survives freezing well
- Can survive when freeze-dried with a protein stabilizer for decades
- Inactivated by solvents like ether, disinfectants, by acids (pH<5), bases (pH>10), and by UV and visible light.
MV is heat sensitive but can survive freezing well (T/F)
True
Transmission for MV
Mode of transmission
Large respiratory droplet
Airborne
Can also infect via the eye and multiply in the conjunctivae
Most infectious in early stage before rash appears but can still be transmitted a week after rash is gone
Incubation period (asymptomatic) - MV
Incubation period lasts between 7 – 10 days
Droplet nuclei - define
Aerosols formed from the evaporation of respiratory droplets.
Generally smaller than 5 μm in diameter.
Formed by the “dried residua of larger respiratory droplets”.
MV pathogenesis
- Transmission via respiratory droplets or aerosolized small droplet nuclei
- Enters cells; can start infection anywhere along respiratory tract from nose to lower airways
- Along the mucociliary epithelium (cilia of mucous membranes in tissues of resp system), dendritic cells can poke through tight junctions to pull in measles cells from lumen (space inside tubular structure)
- MV uses glycoproteins H & F to bind to dendritic cell receptors
In the alveolar space, macrophages can be infected with measles virus - Both DCs and MACs carry MV to lymph nodes; MV now infects lymphocytes (T and B cells)
- They replicate making more measles viruses - amplification
- Spleen and tonsils become infected due to lymphocytes moving to secondary lymphoid organs
- MV can disseminate to skin, resp tract, liver, brain, intestines
- Infected lymphocyte brings MV to basal side of epithelial cells, MV replicates inside cell and exits via budding on apical side
- Damaged epithelial cells cause irritation and virus is expelled by coughing and sneezing
MV causes transient immunosuppression in what ways?
- Inhibits toll like receptor signalling
- inhibits synthesis and signalling of interferons
- Causes lymphopenia (low lymphocyte counts due to infection of lymphocyte cells)
- Interferes with antigen presentation to T cells thus T cell activation
Denoting the period between the appearance of initial symptoms and the full development of a rash or fever - definition for what term?
Prodromal
Timeline of signs and symptoms for MV
Incubation : 7-10 days Prodromal : before rash, after incubation -- Fever 2-10 days -- Cough 2-16 days -- Coryza 2-6 days -- Conjunctivitis 2-6 days Koplik spots 2-4 days (lesions on buccal mucosa) - appears 4 days before skin rash and resolve before skin rash is seen Rash 4-8 days
Skin rash is associated with T cells attacking infected epithelial cells in small BVs. After 1-2 days it’s difficult to isolate replicating MV.
Many clinical signs and symptoms start to resolve also.
All except cough resolve.
Timeline of virus involvement inside host
Virus growth in lymph tissue (1-5 days) Virus goes to body surface (3-6 days) Virus grows on body surface (6-10 days) Respiratory disease (9-14 days) Infectious period (8-16 days)
Antibody titer = low for infectious period but high for every other aspect
People with measles are contagious for _ ____ before and at least _ ____ after the ____ begins
People with measles are contagious for 1 week before and at least 4 days after the rash begins
Other signs and symptoms of MV
Depends on where virus infects
Infection of intestinal epithelial cells:
Diarrhoea, vomiting, abd pain
Dissemination of infected lymphocytes Cervical lymphadenopathy (enlarged lymph nodes), splenomegaly (enlarged spleen)
Infection of mucosal epithelial cells
Pharyngitis (sore throat)
Infection of resp epithelial cells
Viral pneumonia/bronchiolitis
Encephalitis (inflammation of brain tissue)
Complications - MV
Secondary bacterial infections
Pneumonia
Otitis media (inflammation of middle ear) or any other resp tract infection
Subacute schlerosing pan encephalitis (SSPE)
is very uncommon
- chronic infection where virus multiplies in the
brain with the expression of a limited repertoire of
virus genes
- Risk factor - acquiring MV before 2 yrs old
- Occurs 4-8 yrs after contracting acute measles infection
Lab ID
Specimens: nasal secretions, nasopharygneal aspirate, urine
- Direct virus demonstration
In smears of nasal secretions - intranuclear inclusion bodies and syncytial giant cells
Enzyme Immunoassay (EIA) can be used if needed, to detect IgM or IgG levels
Treatment - MV
No treatment, only supportive care (treat symptoms)
Vitamin A supplementation (reduces morbidity)
Ribavirin (reduces complications)
Vaccines - MV
Both live and killed vaccines exist.
Vaccination with the live attenuated vaccine has
been practiced in the US since the 1960’s with a
dramatic decline in the incidence of the disease,
but has only been used more recently in the UK.
Trivalent (3’s) live attenuated vaccine (MMR) usually
given - all of these viruses best avoided during
pregnancy!
When should 2nd dose of MMR vaccine be given?
• 2nd dose between 5-19 years of age
No large preschool-type outbreak of MV has been reported since 1992 (T/F)
True
Report of MV prevlance in US, UK, Latin America and Caribbean
March of 2000, CDC concluded that Measles are no longer an epidemic in the U.S.
• All cases are importations
• Europe and Asia
Pan American Health Organization
• measles incidence is now very low in Latin America and the Caribbean
81% vaccination rate in a community is needed to avoid virus circulation outbreaks (T/F)
False; 93% vaccination rate in a community is needed to avoid virus circulation outbreaks
