Viruses Associated with Respiratory Infections

Syndrome Commonly Associated Less Commonly

Viruses Associated Viruses

Coryza Rhinoviruses, Influenza,

Coronaviruses Parainfluenza viruses,
Enteroviruses,
Adenoviruses
Influenza Influe Influenza viruses Parainfluenza viruses,
Adenoviruses
Croup Parainfluenza viruses Influenza virus, RSV,
Adenoviruses
Bronchiolitis RSV Influenza,
Parainfluenza viruses,
Adenoviruses
Bronchopneumonia Influenza virus, RSV, Parainfluenza viruses,
Adenoviruses Measles, VZV, CMV
Virus Culture Antigen detection
Rhinovirus Yes No
Coronavirus Research only Yes
Adenovirus Yes Yes
Parainfluenza Yes Yes
RSV Yes Yes
IF; EIA

Specimens: nasopharyngeal aspirate; nasal wash

nasopharyngeal swab; throat swab;
tracheal aspirate; bronchoaveolar lavage fluid
 Common Cold Viruses
• Common colds account for one-third to one-
half of all acute respiratory infections in
humans.
• Rhinoviruses are responsible for 30-50% of
common colds, coronaviruses 10-30%.
• The rest are due to adenoviruses, enteroviruses,
RSV, influenza, and parainfluenza viruses,
which may cause symptoms indistinguishable
to those of rhinoviruses and coronaviruses.
• Summer colds: enteroviruses
• Fall colds: Rhinoviruses
• Winter colds: corona and adeno
Rhinoviruses
Family: Picornaviridae; Genus: Enterovirus
Species: Human rhinovirus A (75 serotypes)
B (25 serotypes)
C (6; unculturable in vitro)
many more rhinoviruses (mostly of type C) were identified in clinical
specimens. (2012: 148 HRV types had been found circulating in the
human population)
ssRNA (+) virus
acid-labile
Receptors: Major (ICAM-1); Minor (LDL receptor)
HRV87 alone uses an unidentified sialoprotein as receptor
optimum growth temperature of 33°C
Pleconaril: blocking attachment & uncoating
 Uninfected primary Primary human fibroblasts
human fibroblasts infected with human rhinovirus 16

Virus isolation -The identity can be confirmed by acid lability tests. (pH3)
Rhinoviruses are best isolated in human embryo lung fibroblasts eg. MRC-5, or
a sensitive continuous cell line such as Ohio HeLa.
Samples should be inoculated into triplicates and rolled at 33oC. The virus CPE,
which consists of the rounding of cells similar to that induced by enteroviruses
should appear within 8 days of inoculation
Ag drift
 Parainfluenza Virus

• ssRNA virus
• enveloped, pleomorphic
morphology
• 5 serotypes: 1, 2, 3, 4a and
4b
• No common group antigen
• Closely related to Mumps
virus

(Linda Stannard, University of Cape Town, S.A.)

Mononegavirale (2015 ICTV)
Bornaviridae: borna disease virus (nuclear replication)
Filoviridae
Paramyxoviridae
Henipavirus (Hendra, Nipah)
Mobillivirus (Measles morbillivirus)
Respirovirus
Human respirovirus 1 & 3: human parainfluenza virus 1 & 3
Rubulavirus:
Human rubulavirus 2 & 4: Human parainfluenza virus 2 & 4
mumps rubulavirus
Pneumpviridae
Metapneumovirus: human metapneumovirus
Orthopneumovirus: human orthopneumovirus (RSV)
Rhabdoviridae
Paramyxoviridae
Paramyxovirinae
Respirovirus: Human parainfluenza virus 1 & 3 HN& F
Morbillivirus: Measles virus H & F
Rubulavirus: Human parainfluenza virus 2 & 4 HN & F
Mumps virus HN & F
Henipavirus: Hendra virus, Nipah virus G & F
Pneumovirinae (2015, Pneumoviridae)
Human metapneumovirus G & F
Respiratory syncytia virus G & F
 Laboratory Diagnosis
• Detection of Antigen - a rapid diagnosis can be made by
the detection of parainfluenza antigen from
nasopharyngeal aspirates and throat washings.
• Virus Isolation - virus may be readily isolated from
nasopharyngeal aspirates and throat swabs.
• primary monkey kidney and continuous diploid human
fibroblasts are usually used. Alternatively, LLC-MK2 with
trypsin (2-3 mg/mL) added to the media can be used. It has been
shown that proteases are necessary for parainfluenza virus
replication, and it is hypothesized that proteases present in
primary cell cultures are absent in continuous cell lines. HEK
cells are also sensitive to parainfluenza viruses. The majority of
parainfluenza viruses (except with HPIV-2), do not produce CPE
in cell culture.
• Serology - a retrospective diagnosis may be made by serology.
The following are clinical conditions caused by the various HPIV types
Croup - HPIV-1, HPIV-2, (rare HPIV-3) seal cough
Bronchitis - HPIV-1, HPIV-3 (major)
Minor upper respiratory tract disease - HPIV-1, HPIV-3, HPIV-4

HPIV-2 and HPIV-3 infection in humans is known to induce

expression of intercellular adhesion molecule-1 (ICAM-1) in tracheal
and other cells of the respiratory tract. These molecules serve as
receptors for rhinoviruses, thus paving the way for rhinoviral
superinfection.
 Management

• No specific antiviral chemotherapy available.

• Severe cases of croup should be admitted to hospital
and placed in oxygen tents.
• No vaccine is available.
 Respiratory Syncytial Virus (RSV)
Human orthopneumovirus
• ssRNA eveloped virus.
• belong to the genus Pneumovirus of the Paramyxovirus
family.
• Considerable strain variation exists, may be classified into
subgroups A and B by monoclonal sera.
The two subgroups show different properties in several
structural proteins; G, F, N, M and P, the major antigenic
differences occurring in the G and F proteins.
• Both subgroups circulate in the community at any one
time.
• Causes a sizable epidemic each year.
subtype B: asymptomatic
subtype A: more severe clinical disease
 Infants at Risk of Severe Infection
1. Infants with congenital heart disease - infants who were
hospitalized within the first few days of life with
congenital disease are particularly at risk.
2. Infants with underlying pulmonary disease - infants with
underlying pulmonary disease, especially
bronchopulmonary dysplasia, are at risk of developing
prolonged infection with RSV.
3. Immunocompromized infants - children who are
immunosuppressed or have a congenital
immunodeficiency disease may develop lower
respiratory tract disease at any age.
 Laboratory Diagnosis
• Detection of Antigen - a rapid diagnosis can be made by the
detection of RSV antigen from nasopharyngeal aspirates. A rapid
diagnosis is important because of the availability of therapy
several ELISA kits are available

• Virus Isolation - virus may be readily isolated from

nasopharyngeal aspirates. However, this will take several days.
Human heteroploid cells, such as HEP-2 and HeLa generally
provide the best tissue culture for the isolation of RSV.
RSV in Hep-2: no Calcium medium, Fusion protein decreased
no syncytia
• Serology - a retrospective diagnosis may be made by serology.
CFTs are less sensitive than neutralization and ELISA assays.
Syncytial formation caused by
RSV in cell culture.
 Treatment and Prevention
• Aerosolised ribavirin can be used for infants with
severe infection, and for those at risk of severe disease.

• There is no vaccine available.

• RSV immunoglobulin can be used to protect infants at

risk of severe RSV disease.
Human metapneumovirus (HMPV): Paramyxoviridae,
pneumovirus subfamily, was first isolated in the Netherlands in
2001
The genomic organisation of hMPV is analogous to RSV, however hMPV lacks
the non-structural genes, NS1 and NS2.
major genetic lineages (G protein):
subtypes A (A1, A2) and B (B1, B2)

acute respiratory infection; particularly in children;

it has phenotypic and clinical characteristics that are similar to
those of respiratory syncytial virus (RSV)

hMPV replicates slowly in primary cynomolgus monkey kidney cells

and poorly in Vero cells and A549 cells (a human respiratory
epithelial cell line). HMPV can be isolated in conventional cell cultures
such as LLC-MK2, the appearance of recognizable cytopathic effects
can take 2 weeks or more.
RT-PCR
 Adenovirus
• ds DNA virus
• non-enveloped
• At least 51 serotypes are
known
• classified into 6 subgenera:
A to F
• Penton base: cytotoxicity
• Fiber: type-specific
• hemagglutination

(Linda Stannard, University of Cape Town, S.A.)

 Clinical Syndromes

1. Pharyngitis 1, 2, 3, 5, 7
2. Pharyngoconjunctival fever 3, 7
3. Acute respiratory disease of recruits 4, 7, 14, 21
4. Pneumonia 1, 2, 3, 7
5. Follicular conjunctivitis 3, 4, 11
6. Epidemic keratoconjunctivitis 8, 19, 37
7. Pertussis-like syndrome 5
8. Acute haemorrhaghic cystitis 11, 21
9. Acute infantile gastroenteritis 40, 41
10. Intussusception 1, 2, 5
[Link] disease in AIDS and other immunocompromized
patients 5, 34, 35
12. Meningitis 3, 7
 Treatment and Prevention
• There is no specific antiviral therapy.

• A vaccine is available against Adult Respiratory

Distress Syndrome. It consists live adenovirus 4, 7, and
21 in enterically coated capsules. It is given to new
recruits into various arm forces around the world.
Human bocavirus: Parvoviridae; genus Bocavirus
identified in Sweden, 2005
The virus was identified in clinical specimens from infants and
children with respiratory tract illness.
HBoV infection occurs predominantly during the winter season
and that children <2 years of age are most at risk.
A multiplex RT-PCR assay kit under dual priming oligonucleotide
system (DPO) that is used to detect 12 common viruses causing
respiratory tract infections in children has recently become
available.

Yoo SJ, Kuak EY, Shin BM. Detection of 12 respiratory viruses with two-set multiplex
reverse transcriptase-PCR assay using a dual priming oligonucleotide system.
Korean J Lab Med. Dec 2007;27(6):420-7.
Dual priming oligonucleotide system
Polydeoxyinosine linker

Poly(I) linkers

18-25 NT 6-12 NT

1, 3: long pr
2, 4: DPO
Chun J et al. Nucl. Acids Res. 2007;35:e40