Respiratory Viruses

Titiek Djannatun
Bagian Mikrobiologi Fakultas kedokteran
Universitas YARSI
Viruses Associated with
Respiratory Infections
Syndrome Commonly Associated Viruses Less Commonly Associated Viruses
Corza Rhinoviruses, Coronaviruses Influenza and parainfluenza viruses,
enteroviruses, adenoviruses
Influenza Influenza viruses Parainfluenza viruses, adenoviruses
Croup Parainfluenza viruses Influenza virus, RSV, adenoviruses
Bronchiolitis RSV Influenza and parainfluenza viruses,
adenoviruses
Bronchopneumonia Influenza virus, RSV, Adenoviruses Parainfluenza viruses, measles, VZV, CMV
INFEKSI VIRUS PADA SALURAN
PERNAPASAN
Virus Penyebab yang Paling Sering
Sindroma Gejala Utama Bayi Anak-anak Dewasa
Flu Hidung tersumbat,
pilek
Rino
Adeno
Rino
Adeno
Rino
Corona
Faringitis Sakit tenggorokan Adeno
Herpes Simplex
Adeno
Coxackievirus

Adeno
Coxackievirus
Laringitis, batuk dengan
sesak napas
Serak, batuk Parainfluenza
Influenza
Parainfluenza
Influenza
Parainfluenza
Influenza
Trakeobronkitis Batuk Parainfluenza
Influenza
Parainfluenza
Influenza
Influenza
Adeno
Bronkiolitis Batuk, sesak napas Sinsitial pernapasa
Parainfluenza
Jarang

Jarang
Pneumonia Batuk, nyeri dada Sinsitial pernapasan
Influenza
Influenza
Parainfluenza
Influenza
Adeno
Common Cold (Rhinitis/Selesma)
Virus Tipe
Reseptor pd sel
hospes
Penyakit
Rhinovirus (> 100 tipe) Beberapa tipe ICAM-1 Common cold
Coxsackie virus A (24
tipe)
Terutama A21 ICAM-1 Common cold, herpangina
Virus Influenza Beberapa tipe glikoprotein Bisa menyebabkan infeksi
LRT
Virus Parainfluenza 1, 2, 3, 4 glikosida Dapat menyerang laring
RSV (2 tipe) Reseptor Protein G Bisa menyebabkan infeksi
LRT
Coronavirus semua glikoprotein Common cold, SARS
Adenovirus (41 tipe) 5 - 10 Reseptor Penton Faringitis, bronchitis,
conjunctivitis
Echovirus (34 tipe) 4, 9, 11, 20, 25 - Common cold
Viral Pharingitis
Rhinovirus, Coronavirus Common cold
Adenovirus (3, 4, 7, 14, 21) Pharyngoconjunctival fever
Parainfluenza virus > Berat dari CC
Influenza virus, CMV Tidak selalu ada
Coxsackie A dan enterovirus lain Herpangina
Epstein-Barr virus Glandular fever
Herpes simplex virus tipe 1 Ulkus dan vesikel pada palatum
Viral Pneumonia
Virus Manifestasi klinis
Influenza A dan B Pneumonia primer
Parainfluenza (tipe 1-4) Croup, Pneumonia pada anak
Measles Pneumonia sekunder
RSV Bronchiolitis (bayi)
Adenovirus Pharyngoconjunctival fever,
pharyngitis, atypical pneumonia
CMV Interstitial pneumonia
Coronavirus SARS
Influenzae Viruses
An Overview
Influenza Virus
RNA virus, genome consists of 8
segments
enveloped virus, with
haemagglutinin and neuraminidase
spikes
3 types: A, B, and C
Type A undergoes antigenic shift
and drift.
Type B undergoes antigenic drift
only and type C is relatively stable
(Courtesy of Linda Stannard,
University of Cape Town, S.A.)
NOMENKLATUR
FAMILIA ORTHOMYXOVIRIDAE
GENUS INFLUENZAVIRUS A
INFLUENZAVIRUS B
INFLUENZAVIRUS C
SIFAT-SIFAT PENTING :
VIRION BULAT, PLEOMORFIK,HELIKS, 80-120 nm
SS RNA, BERSEGMEN (8MOL), POLARITAS - ,
REPLIKASI TRANKRIPSI : NUKLEUS; MATURASI : M
PLASMA
MENYEBABKAN EPIDEMI DI SELURUH DUNIA

NOMENKLATUR
PERBEDAAN ORTHOMYXOVIRUS &
PARAMYXOVIRUS
SIFAT-SIFAT ORTHOMYXOVIRUS PARAMYXOVIRUS
PENYAKIT PD MANUSIA Influenza tipe A, B, C Parainfluenza 1-4, peny.
Sinsitium pernafasan, gondong,
campak
PENGATURAN GENOM ss RNA DLM 8 BAGIAN ss RNA DLM 1BAGIAN
HELIKS
RIBONUKLEOPROTEIN
BERDIAMETER 9 nm BERDIAMETER18 nm

RNA DLM NUKLEOKAPSID PEKA THDP RNase RESISTEN THDP RNase

FUSI VIRUS -SEL ENDOSOM MEMBRAN PLASMA
TRANSKRIPSI NUKLEUS SITOPLASMA
PEMILIHAN GENETIK SERING JARANG
PERUBAHAN GENETIK TINGGI RENDAH
PERBEDAAN INFLUENZA A, B DAN C
TIPE A TIPE B

TIPE C

DERAJAT PENYAKIT ++++ ++ +
HEWAN RESERVOIR YA TIDAK TIDAK
PANDEMIK PADA MANUSIA YA TIDAK

TIDAK

EPIDEMIK PADA MANUSIA

YA YA TIDAK
(SPORADIK)
PERUBAHAN ANTIGENIK SHIFT, DRIFT DRIFT DRIFT
GENOM BERSEGMEN YA YA YA
AMANTADINE, RIMANTIDINE SENSITIF TIDAK
BEREFEK
TIDAK
BEREFEK
ZANAMIVIR SENSITIF SENSITIF
GLIKOPROTEIN PERMUKAAN 2 2 1
STRUKTUR ANTIGEN
HA 15 SUBTIPE
NA 9 SUBTIPE
STRUKTUR ANTIGEN
STRUKTUR ANTIGEN
HEMAGLUTININ
KEMAMPUAN MENGAGLUTINASI ERITROSIT
FUNGSI MEDIASI ADHESI VIRUS SEL HOSPES
FASILITASI PENETRASI VIRUS

NEURAMINIDASE
MERUSAK PERTAHANAN MUKOSA
MEMBANTU BUDDING VIRAL & PELEPASAN VIRUS

MERUPAKAN TONJOLAN GLIKOPROTEIN (FAKTOR
VIRULENSI VIRUS ) BERUBAH TIBA2/SEC GRADUAL
TERHINDAR DARI KEKEBALAN MEMORI SEL
VARIABILITAS TINGGI
MORFOLOGI VIRUS
Influenza A Virus

Undergoes antigenic shifts and antigenic drifts with
the haemagglutinin and neuraminidase proteins.
Antigenic shifts of the haemagglutinin results in
pandemics. Antigenic drifts in the H and N
proteins result in epidemics.

Usually causes a mild febrile illness.

Death may result from complications such as
viral/bacterial pneumonia.
Epidemiology
Pandemics - influenza A pandemics arise when a virus
with a new haemagglutinin subtype emerges as a result of
antigenic shift. As a result, the population has no immunity
against the new strain. Antigenic shifts had occurred 3
times in the 20
th
century.

Epidemics - epidemics of influenza A and B arise through
more minor antigenic drifts as a result of mutation.
Past Antigenic Shifts
1918 H1N1 Spanish Influenza 20-40 million deaths

1957 H2N2 Asian Flu 1-2 million deaths

1968 H3N2 Hong Kong Flu 700,000 deaths

1977 H1N1 Re-emergence No pandemic


At least 15 HA subtypes and 9 NA subtypes occur in nature.
Up until 2007, only viruses of H1, H2, H3 and H5 and NA
(N1,N2) are known to infect and cause disease in humans.

Influenzae A viruses
The Influenzae virus can subdivided into different serotypes
base on Antibody response to these viruses. The serotypes
that have been confirmed in humans ordered by the number
of known human pandemic deaths are:
H1N1 spanish flu
H2N2 Asian Flu
H3N2 Hongkong flu
H5N1 Pandemic threat in 2007-2008 flu season
H7N7 Zoonotic potential
H1N1 endemic in human and pigs
H9N2, H7N2, H7N3, H10N7


Avian Influenza
H5N1
An outbreak of Avian Influenza H5N1 occurred in Hong Kong in 1997 where 18
persons were infected of which 6 died.
The source of the virus was probably from infected chickens and the outbreak
was eventually controlled by a mass slaughter of chickens in the territory.
All strains of the infecting virus were totally avian in origin and there was no
evidence of reassortment.
However, the strains involved were highly virulent for their natural avian hosts.

H9N2
Several cases of human infection with avian H9N2 virus occurred in Hong Kong
and Southern China in 1999.
The disease was mild and all patients made a complete recovery
Again, there was no evidence of reassortment
VARIASI ANTIGENIK
ANTIGENIC DRIFT

MUTASI KONSTAN PADA GLIKOPROTEIN

SERING PADA SISI TEMPAT GLIKOPROTEIN
BINDING AB, JARANG PADA SISI UNTUK
MELEKAT PADA SEL HOSPES

PERUBAHAN SECARA GRADUAL KOMPOSISI ASAM
AMINO MENURUN KEMAMPUAN SEL MEMORI SEL
HOSPES UNTUK VIRUS
VARIASI ANTIGENIK
ANTIGENIC SHIFT GENETIC REASSORTMENT

PERTUKARAN DARI 1 GEN (GENOM VIRUS T/D 8
GEN DIKODE SS RNA) DENGAN GEN / STRAND
DARI VIRUS INFLUENZAE YANG LAIN

SEBABKAN PANDEMIK
VARIASI ANTIGENIK
Theories Behind Antigenic Shift
1. Reassortment of the H and N genes between human and
avian influenza viruses through a third host. There is
good evidence that this occurred in the 1957 H2N2 and
the 1968 H3N2 pandemics.
2. Recycling of pre-existing strains this probably occurred
in 1977 when H1N1 re-surfaced.
3. Gradual adaptation of avian influenza viruses to human
transmission. There is some evidence that this occurred
in the 1918 H1N1 pandemic.
Reassortment

Avian H3 Human H2
Human H3
Reassortment
Reassortment
PATOGENESA
TRANSMISI INHALASI (KONTAK DIREK/INDIREK)

DROPLETS
AEROSOLS
FOMITES

MASA INKUBASI 18 72 JAM
VIRUS ADA PADA SEKRESI TRACHEA/HIDUNG 24-48 JAM
SETELAH GEJALA
PATOGENESA
RECOVERY & PROTECTION SEL HOSPES
VIRAL REPLIKASI
GEJALA DAN KOMPLIKASI
INFLUENZA TANPA KOMPLIKASI:
DEMAM (38 40
0
C)
MIALGIA, HEADACHE
OCULAR SYMPTOM FOTOPOBIA, BERAIR, ACHE
BATUK KERING, NASAL DISCHARGE

PULMONARY COMPLICATIONS, SEQUELE:
CROUP (LARYNGOTRACHEOBRONCHITIS AKUT) PADA
ANAK2
PRIMARY INFLUENZA VIRUS PNEUMONIA
INF SEK BAKTERI S. pneumonia, S. aureus, H. influenzae
GEJALA DAN KOMPLIKASI
NON-PULMONARY COMPLICATIONS:

MYOSITIS JARANG, PADA ANAK STLH INF
TIPE B
CARDIAC COMPLICATIONS
ENCEPHALOPATHY
SINDROM REYE
SINDROM GUILLAIN BARRE
DIAGNOSA DAN PENCEGAHAN
DIAGNOSA :
ISOLASI DAN IDENTIFIKASI VIRUS 3 10 HARI
SROLOGI PCR, ELISA, IMMUNOFLUORESCENSI

PENCEGAHAN :
VAKSINASI EFEKTIF 70 90%
VIRUS MATI YANG DITUMBUHKAN PADA TET
(MENGANDUNG 3 MACAM VIRUS) USIA 6 BLN

FLUMIST NASSAL VACCINE
3 STRAIN ATTENUATED VIRUS
MERANGSANG KEKEBALAN MUKOSA (SECRETORY)
AMAN & EFEKTIF UNTUK ORANG USIA 5 49 TAHUN
TIDAK UNTUK INDIVIDU YANG IMUN RENDAH

Laboratory Diagnosis
Detection of Antigen - a rapid diagnosis can be made by
the detection of influenza antigen from nasopharyngeal
aspirates and throat washings by IFT and ELISA

Virus Isolation - virus may be readily isolated from
nasopharyngeal aspirates and throat swabs.

Serology - a retrospective diagnosis may be made by
serology. CFT most widely used. HAI and EIA may be
used to give a type-specific diagnosis

Management
Amantidine is effective against influenza A if given early in
the illness. However, resistance to amantidine emerges
rapidly
Rimantidine is similar to amantidine but but fewer
neurological side effects.
Ribavirin is thought to be effective against both influenza A
and B.
Neuraminidase inhibitors are becoming available. They are
highly effective and have fewer side effects than amantidine.
Moreover, resistance to these agents emerge slowly
Prevention
Inactivated split/subunit vaccines are available against
influenza A and B.
The vaccine is normally trivalent, consisting of one A
H3N2 strain, one A H1N1 strain, and one B strain.
The strains used are reviewed by the WHO each year.
The vaccine should be given to debilitated and elderly
individuals who are at risk of severe influenza infection.
Amantidine can be used as an prophylaxis for those who
are allergic to the vaccine or during the period before the
vaccine takes effect.
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.)
PENDAHULUAN
TAKSONOMI :
FAMILIA PARAMYXOVIRIDAE
GENUS PARAMYXOVIRUS
SPESIES HUMAN PARAINFLUENZA VIRUS

AGEN PENYEBAB INFEKSI PADA SALURAN
PERNAFASAN BAYI DAN ANAK KECIL USIA DI
BAWAH 5 TAHUN
SIFAT-SIFAT PENTING
VIRION BULAT, PLEOMORFIK, DIAMETER 150-300 nm,
NUKLEOKAPSID HELIX 18 nm
GENOM SS RNA, TIDAK BERSEGMEN, LURUS, - , 16 20
KB
PROTEIN 6 PROTEIN STRUKTURAL
ENVELOPE GLIKOPROTEIN :
HEMAGLUTININ (HN) KADANG MEMBAWA
AKTIVITAS NEUROAMINIDASE
FUSI (F) RINGKIH
REPLIKASI SITOPLASMA, BERTUNAS DI M PLASMA
CIRI KHAS ANTIGEN STABIL, PARTIKEL LABIL JUGA
SANGAT INFEKSIUS

STRUKTUR DAN KOMPOSISI
MIRIP VIRUS INFLUENZA, UKURAN LEBIH BESAR
GENOM TIDAK BERSEGMEN STABIL
PROTEIN :
6 PROTEIN STRUKTIRAL
3 PROTEIN BERSATU RNA-NUKLEOPROTEIN (NP/N)
PROTEIN P & L AKTIVITAS POLIMERASE VIRUS DLM
TRANSKRIPSI DAN REPLIKASI
3 PROTEIN PEMBENTUK ENVELOPE
PROTEIN MATRIX (M) MENDASARI ENVELOPE
GLIKOPROTEIN HN / H AKTIVITAS HEMAGLUTININ &
NEURAMINIDASE
GLIKOPROTEIN F FUSI MEMBRAN & AKTIVITAS
HEMOLISIN

VIRAL STRUCTURE
Viral Life Cycle (RER=Rough endoplasmic
reticulum)
SPECIES PARAMYXOVIRUS
PARAINFLUEZAE (TIPE 1-4)
CROUPS (TIPE 1&2), PNEUMONIA PADA
ANAK < 5 THN
PENY SAL PERNAFASAN ATAS (SERING
SUBKLINIK) PADA ANAK & DEWASA
TIPE 1 VIRUS SENDAI
COMMOND COLD
SPECIES PARAMYXOVIRUS
Virus Measles :
PNEUMONIA DI NEGARA BERKEMBANG
SEBABKAN GIANT CELL PNEUMONIA
VIRUS REPLIKASI PADA SAL PERNAFASAN
BAWAH KERUSAKAN SEL INFEKSI
SEKUNDER DENGAN BAKTERI
PNEUMONIA
MALNUTRISI RESPON IMMUN BURUK
KOPLIKS SPOT PADA MUKOSA BUCCAL




SPECIES PARAMYXOVIRUS
VIRUS MUMPS :
GONDONG, PAROTITIS, ORCHITIS

VIRUS SINSITIA PERNAFASAN :
PNEUMONIA
INFEKSI VIRUS
PATOGENESA & PATOLOGI
IMUNITAS
DIAGNOSA LABORATORIUM
EPIDEMIOLOGI
PENGOBATAN DAN PENCEGAHAN
Clinical Manifestations
Croup (laryngotraheobroncitis) - most common
manifestation of parainfluenza virus infection. However
other viruses may induce croup e.g. influenza and RSV.
Other conditions that may be caused by parainfluenza
viruses include Bronchiolitis, Pneumonia, Flu-like
tracheobronchitis, and Corza-like illnesses.
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.

Serology - a retrospective diagnosis may be made by
serology. CFT most widely used.
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)
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.
Both subgroups circulate in the community at any one
time.
Causes a sizable epidemic each year.
Clinical Manifestations
Most common cause of severe lower respiratory
tract disease in infants, responsible for 50-90% of
Bronchiolitis and 5-40% of Bronchopneumonia
Other manifestations include croup (10% of all
cases).
In older children and adults, the symptoms are
much milder: it may cause a corza-like illness or
bronchitis.
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

Virus Isolation - virus may be readily isolated from
nasopharyngeal aspirates. However, this will take several
days.

Serology - a retrospective diagnosis may be made by
serology. CFT most widely used.
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.
Adenovirus
ds DNA virus
non-enveloped
At least 47 serotypes are
known
classified into 6 subgenera:
A to F

(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
11. Severe disease in AIDS and other immunocompromized patients 5,
34, 35
12. Meningitis 3, 7
Laboratory Diagnosis
Detection of Antigen - a rapid diagnosis can be made by
the detection of adenovirus antigen from nasopharyngeal
aspirates and throat washings.

Virus Isolation - virus may be readily isolated from
nasopharyngeal aspirates, throat swabs, and faeces.

Serology - a retrospective diagnosis may be made by
serology. CFT most widely used.
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.
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.
Rhinovirus
ssRNA virus
Belong to the picornavirus
family
ssRNA virus
acid-labile
at least 100 serotypes are
known
Reconstructed Image of rhinovirus particle (Institute
for Molecular Virology)
Coronavirus
ssRNA Virus
Enveloped, pleomorphic
morphology
2 serogroups: OC43 and
229E
Pendahuluan Coronavirus
Virus RNA polaritas positif, berenvelop
Coronavirus manusia menyebabkan
Common cold (rhinitis, selesma) dan
gastroenteritis pada bayi.
Corona virus yang ditemukan tahun 2003
SARS Associated Coronavirus infeksi
saluran nafas bawah.
Coronavirus sulit dikultur
Sifat Coronavirus
Genom terdiri atas RNA-ss tidak
bersegmen, positif-sense
Envelope mempunyai tonjolan
membentuk korona
Replikasi di sitoplasma
Famili Coronaviridae
Genus Coronavirus dan Totovirus
Human Coronavirus ada 2 strain 229E
dan OC43
SARS Associated Coronovirus
BACK
Infeksi pada Manusia
Virus mempunyai tropisme pada sel epitel saluran
nafas dan pencernaan.
Virus manusia biasanya terbatas pada sal nafas
atas, kecuali SARS Coronavirus yang
menyebabkan pneumonia berat.
Manifestasi klinis:
Common cold (seperti rhinovirus)
Gastroenteritis partikel virus pernah ditemukan dari
feses
SARS virus berasal dari non-human
Imunitas
Imunitas yang terbentuk sesudah infeksi
tidak bersifat mutlak
Ab terpenting adalah Ab terhadap protein
permukaan virus
95% pasien SARS membentuk Ab thd Ag
virus (immunofluoresens/ELISA); serum
konvalesens diambil > 28 hari sesudah
gejala timbul
Pemeriksaan Laboratorium
Deteksi Ag dan As. Nukleat
ELISA
Mikroskop elektron, sampel dari feses
PCR, sampel dari sekret sal nafas atau feses
Kultur:
Sukar dilakukan
SARS virus sel Vero dari sampel orofaring
Serologi:
Konfirmasi diagnosis dengan ELISA
Epidemiologi
Coronavirus tersebar di seluruh dunia
Penyebab 15-30% kasus CC
SARS:
Penularan dengan kontak dekat
Dikenal adanya super spreader (seperti pada
infeksi rubella, Ebola, dan tbc) tergantung
faktor hospes, virus dan lingkungan.
Terapi dan Pencegahan
Tidak ada terapi dan vaksin spesifik untuk
Coronavirus
Kontrol SARS efektif dengan cara:
Isolasi penderita
Karantina orang yang kontak dengan penderita
Pembatasan kunjungan (travel restriction)
Pemakaian alat pelindung (masker, goggles,
baju, sarung tangan) bagi tenaga medis
BACK
Common Cold
Disebabkan oleh > 200 tipe virus
Rhinovirus, Coronavirus, adenovirus, influenza
virus, parainfluenza virus, coxsackie virus,
echovirus, RSV
CC bisa menjadi faktor predisposisi infeksi
sekunder, e.g. bakteri
Faktor virulensi adalah adhesin pada permukaan
partikel virus
Diagnosis Lab: umumnya tidak perlu
BACK
SARS VACCINE
Attenuated vaccine
SARS VACCINE
Drugs Development