The document discusses Myxoviruses, which are RNA viruses that infect the respiratory mucosa. It specifically focuses on Orthomyxoviruses like influenza virus and Paramyxoviruses such as parainfluenza virus, respiratory syncytial virus, measles virus, and mumps virus. It provides details on the structure, transmission, pathogenesis, diagnosis, and treatment of these important respiratory viruses.

2.  Myxo – Mucous/mucin
 Myxovirus –
 RNA Virus infecting mucous membrane
(respiratory)
 Affinity for certain mucins
 Causing agglutination of red blood cells
 ORTHO (Influenza) & PARA (Others)

4. MYXO VIRUSES
Orthomyxo Paramyxo
Influenza Virus Parainfluenza Virus
Respiratory Syncytial
Measles
Mumps

6.  Spherical/Filamentous/Pleomorphic
 Enveloped (150-300nm)
 RNA ss – Non segmented
 Negative sense genome
 5 subtypes – PIV 1/2/3/4a/4b

8.  HN – Haemagglutinin neuraminidase
 F – Fusion
 M - Matrix (underneath the envelope)
 N/NP – Nucleoprotein
 P – Phosphoprotein
 L – Large RNA Polymerase

10. 1
3
5
2
4
6
8
7

11.  Inhalation – Virus laden droplets
 Incubation
 2-8 days (nasopharyngeal epithelium)
 Further 1-3 days – Spread through tracheobronchial
tree
 Both upper and lower RTI
 Viremia is uncommon in immunocompetent hosts
 Infants/children more commonly affected

12.  Respiratory illness
 Croup (Laryngotracheobronchitis)
 Bronchiolitis
 Pneumonia
 Pharyngitis
 Common cold/rhinitis

13.  Airway inflammation
 Necrosis/sloughing of epithelium
 Oedema/excessive mucous production
 Croup (PIV1,2)
 Peaks between 1-2 yrs of age
 Swelling of vocal cords, larynx, trachea, bronchi
 Obstruction of inflow of air (Stridor)
 LRTI (PIV3)
 Alveolar filling
 Interstitial infiltration

14.  Maternal antibodies usually not protective
 Neutralizing antibodies (protective humoral
immunity)
 HN & F
 May not protect against re-infection
 21 epitopes in PIV1 HN
 20 epitopes in PIV3 F
 Repeated infections needed for full protection
(implications in vaccine development)

15. Specimens: All used successfully
 Throat swab
 nasopharyngeal swab
 nasal wash
 nasal aspirates
Transport
 Swab/2-3ml washings
 VTM (2-3ml) (MEM with 0.5% BSA +
antibacterials/antifungals)
 4 °C
 If delay (Frozen – If delayed >24 hrs)

16. Serological diagnosis
 ELISA/RIA/HI/CFT/WB
 Drawback – cross reactivity among different PIV types
 CFT – least cross reactions (max specificity) but least
sensitive
 ELISA – Most sensitive but least specific
 4 fold rise to any PIV type – significant (even if
heterologous antibodies +ve) – can not tell the subtype
Antigen detection
 Direct immunofluorescence
 Rapid but less sensitive than viral isolation
 Highly specific immune reagents (MAbs)required for
serotype identification

17.  Culture/Isolation
Cell culture
 Primary monkey Kidney cells (best)
 Cynomolgus cell line
 CPE – 4-7 days – syncytia & roundening
 Identification & typing –
IF – most rapid & accurate
EGGS - Poor medium
- Many repeated blind passages needed

18.  Supportive
 Prevent secondary bacterial infections
In vitro trials with antivirals
 Neuraminidase inhibitor – Zanamivir
 Protein synthesis inhibitor – Puromycin
 Ascorbic acid
 Calcium enolate
Novel approach
 Inhibitors of syncytia formation (synthetic peptides
against F protein)
 Several immunostimulators tried (no significant
outcome)

20.  Respiratory syncytial virus is the most
important cause of lower respiratory
tract illness in infants and young
children, usually outranking all other
microbial pathogens as the cause of
bronchiolitis and pneumonia in infants
under 1 year of age.

21.  RNA ss, unsegmented, negative sense
 3 surface proteins
 G – Attachment (No HA & NA activity)
 F – Fusion
 2 matrix proteins
 M, M2
 3 Nucleocapsid proteins
 N, P & L
 F & G – Neutralizing Abs – Imp for vaccine
development

22. F protein
G protein

23.  Most common cause of bronchiolitis
 May also cause –
Pneumonia/croup/pharyngitis/common cold
 Bronchiolitis
 Predominantly in infants
 Peak age – 2-6 months
 >80% cases in 1st year of life
 Often starts with rhinitis
 After 2-3 days – LRT symptoms appear
 Wheezing – Hallmark of bronchiolitis
 Flaring of nostrils, use of accessory muscles.
 Elevated respiratory rate – 50-80breaths / min.
 1/3rd may be afebrile – fever does not indicate
the severity

25. Cell culture
 Nasal swab, throat swab, tracheal aspirates
nasopharyngeal aspirates – All tested for efficiency
 Nasal washes/aspirates – better than swabs
 Cell lines
 Human epithelial (HEp-2) – 8-10 days
 Human lung fibroblast (WI-38 or MRC 5) – 14 days
 Rhesus monkey kidney – 7 days
 CPE - Distinct syncytia formation
- Balled up syncytia become detached & float
freely
 Identification by – IFA (most common)

26. Antigen detection
 ELISA/IF assays
 Several kits available commercially
 IF -Best results with pool of antibodies to
Fusion & Nucleoproteins
- 91 % sensitivity
 ELISA - 79% sensitivity
Antibody detection
 CFT/ELISA
 Poor sensitivity in infants

27.  Bacterial superinfections infrequent – routine
antibiotics not warranted
 Supportive care – fluids/electrolyte monitoring
 Bronchodilators- Conflicting reports, no beneficial
role.
 Antivirals –
Ribavirin - initial reports showed benefit
- findings not confirmed
- considered primarily in severe cases
 RSV-IGIV (RespiGam)
- Passive transfer of specific antibodies
- Prophylactic (premature, congenital
heart disease)

29.  100-150 nm
 RNA ss, negative sense
 Outer envelope proteins
 H –Attachment (CD46, CD150)
 F – Fusion
 M - Matrix

31.  Natural infection only in humans
 Age : 6 months to 5 years old (maternal
antibodies are protective)
 Air-borne transmission
 Highly contagious (90% attack rate in
susceptible individuals)
 Permanent immunity acquired after disease –
single serotype

32. Virus gains access via respiratory tract
It multiplies locally
Spreads to regional lymphoid tissue
Further multiplication occurs
Primary viremia disseminates the virus
Then replicates in the reticuloendothelial system.
A secondary viremia seeds the epithelial surfaces of the body
where focal replication occurs
 skin
 respiratory tract
 conjunctiva.
 Multinucleated giant cells with intranuclear inclusions are seen in
lymphoid tissues throughout the body

34.  Characterized by
 Fever
 URT catarrhal
 koplik’s spots
 Maculopapular rash Seuence:behind the ear→along
thehairline→face→neck→chest→back→abdomen→
limbs→hand and feet(palm,sole)

38.  Bronchopneumonia (most fatal complication)
 Otitis media
 Myocarditis
 Laryngitis
 Neurologic complications:
 Post Infectious Encephalomyelitis (PIE)
1:1000
 After1-3 weeks
Immunological reaction
 Subacute Sclerosing Panencephalitis (SSPE).
1:300,000
After 5-15 years (dormant/persistant infection)
Defective viral replication
High antibody titres in CSF

39. Antigen Detection
 Directly in epithelial cells in respiratory secretions
and urine
 Nucleoprotein detection- The most abundant viral
protein in infected cells
Serological Diagnosis
 fourfold rise in antibody titer between acute-phase
and convalescent-phase sera
 Specific IgM antibody in a single serum specimen
drawn between 1 and 2 weeks after the onset of
rash
 ELISA, HI, and Nt tests all may be used

40. Isolation and Identification of Virus
 Samples
 Nasopharyngeal and conjunctival swabs
 Blood
 Respiratory secretions
 Urine
 Cell lines
 Monkey or human kidney cells
 Lymphoblastoid cell line (B95-a)
 Detection
 Cytopathic effects (multinucleated giant cells containing
both intranuclear and intracytoplasmic inclusion bodies)
take 7–10 days to develop
 Fluorescent antibody staining to detect measles antigens
in the inoculated cultures.

41.  General therapy: rest, nursing and diet
 Symptomatic therapy: fever and cough
 Support therapy : Vitamin A
 Treatment of complications
 Active immunization
 Lived attenuated measles vaccine.

43.  Humans are the only natural hosts
 Acute contagious disease
 More than one-third of all mumps infections
are asymptomatic.
 Primary replication occurs in nasal or upper
respiratory tract epithelial cells.
 Viremia then disseminates the virus to the
salivary glands and other major organ systems.
 Mumps is a systemic viral disease with a
propensity to replicate in epithelial cells in
various visceral organs.

44.  The incubation period -2 weeks to 4 weeks
 A prodromal period of malaise and anorexia
 Rapid enlargement of parotid glands as well as
other salivary glands.
 Hallmark - Nonsuppurative enlargement salivary
glands.
 Virus is shed in the saliva from about 3 days before
to 9 days after the onset of salivary gland swelling.
 Infected individuals who do not exhibit obvious
symptoms (inapparent infections) are equally
capable of transmitting infection.
 Mostly causes a mild childhood disease, but in
adults complications including meningitis and
orchitis are fairly common.

47.  Central nervous system involvement – Aseptic
meningitis (10-30% cases)
 Testes and ovaries may be affected, especially
after puberty.
 Pancreatitis is reported in about 4% of cases

48.  Immunity is permanent after a single infection.
 There is only one antigenic type of mumps
virus
 It does not exhibit significant antigenic
variation
 Antibodies against the HN antigen correlate
well with immunity.(Protective )

49. Serology
 Fourfold or greater rise in antibody titer is
evidence of mumps infection.
 Specific IgM in serum drawn early in illness
strongly suggests recent infection
 The ELISA or HI test is commonly used

50. Isolation and Identification of Virus
 Samples
 Saliva
 Cerebrospinal fluid
 Urine
 Cell line – Monkey Kidney cell line
 Detection
 Cytopathic effects typical of mumps virus consist of
cell rounding and giant cell formation
 Immunofluorescence

51.  There is no specific therapy
 Supportive/symptomatic treatment
 Immunization with attenuated live mumps
virus vaccine is the best approach