OrthomyxovirusesOrthomyxoviruses

80-120 nm, sphericalssRNA, negative senseSegmented (8) genome

Gen products:Gen products: PB2: RNA polymerase; recognise the capPB2: RNA polymerase; recognise the cap PB1-F2: Propaoptotic activityPB1-F2: Propaoptotic activity PB1: RNA pol., endonuclease, elongationPB1: RNA pol., endonuclease, elongation PA: RNA pol.; proteasePA: RNA pol.; protease HA: Surface GP, receptor binding, fusion; major antigenHA: Surface GP, receptor binding, fusion; major antigen NP: RNA binding, RNA synthesis, transport of RNA to NP: RNA binding, RNA synthesis, transport of RNA to

nucleusnucleus NA: Surface GP; neuraminidase activityNA: Surface GP; neuraminidase activity M1: MAtrix protein; export from nucleus; interaction M1: MAtrix protein; export from nucleus; interaction

with vRNP surface glycoproteins; buddingwith vRNP surface glycoproteins; budding M2: Membrane protein; ion channel activity; assemblyM2: Membrane protein; ion channel activity; assembly NS1: Multifunctional protein; agonist of viral IFNNS1: Multifunctional protein; agonist of viral IFN NEP/NS2: Transport of vRNP from nucleusNEP/NS2: Transport of vRNP from nucleus

Unique Features of the Influenza A and B Viruses

Body_ID: B059001

Enveloped virion has a genome of eight unique negative-sense RNA nucleocapsid segments. •Hemagglutinin glycoprotein is the viral attachment protein and fusion protein; it elicits neutralizing, protective antibody responses. •Influenza transcribes and replicates its genome in the target cell nucleus but assembles and buds from the plasma membrane.

The antiviral drugs amantadine and rimantadine inhibit an uncoating step and target the M2 (membrane) protein for influenza A only. •The antiviral drugs zanamivir and oseltamivir inhibit the NA protein of influenza A and B. •The segmented genome promotes genetic diversity caused by mutation and reassortment of segments on infection with two different strains. •Influenza A infects humans, mammals, and birds (zoonosis).

M1, M2 and NP are typespecific M1, M2 and NP are typespecific İnfluenza A, B, and Cİnfluenza A, B, and C

Strains of influenza A virus are classified by Strains of influenza A virus are classified by the following four characteristics: the following four characteristics:

Type (A, B, and C) Type (A, B, and C) Place of original isolation Place of original isolation Date of original isolation Date of original isolation Antigen (HA and NA)Antigen (HA and NA)

Influenza A/New York/07/09 Influenza A/New York/07/09 (H1N1)(H1N1)

Mutations in HA and NA genes Mutations in HA and NA genes Antigenic driftAntigenic drift

Reassorments Reassorments Antigenic shift Antigenic shift

Pandemic Pandemic DAteDAte DeathsDeaths SubtypeSubtypePandemicPandemic SeveritySeverity IndexIndex

AsiaticAsiatic ( (RussianRussian) ) FluFlu

1889–18901889–1890 1 1 millionmillion posibleposible H2N2H2N2 ??

SpanishSpanish FluFlu 1918–19201918–1920 40 to 10040 to 100millionmillion H1N1H1N1 55

AsianAsian FluFlu 1957–19581957–1958 1 to 1.51 to 1.5 millionmillion H2N2H2N2 22

Hong Kong Hong Kong FluFlu 1968–19691968–1969 0.75 to 1 0.75 to 1

millionmillion H3N2H3N2 22

Swine fluSwine flu 2009-20102009-2010 H1N1H1N1

Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, 5th ed. 2000:1829. Modified from Kilbourne ED. Influenza. 1987:274, with permission.

Introduction ofIntroduction ofhypotheticalhypotheticalA HxNx virusA HxNx virus

Significant minor variation A HxNx may Significant minor variation A HxNx may occur at any of these points. Epidemics occur at any of these points. Epidemics may or may not bemay or may not beassociated with such variationsassociated with such variations

Introduction of hypotheticalIntroduction of hypotheticalA HyNy major (new subtype)A HyNy major (new subtype)variant A HxNx disappearsvariant A HxNx disappears

Dis

ease

Inci

denc

eD

isea

se In

cide

nce

Mea

n Po

pula

tion

Ant

ibod

y Le

vel

Mea

n Po

pula

tion

Ant

ibod

y Le

vel

PandemicPandemic

EpidemicEpidemicEpidemicEpidemic

PandemicPandemicInterpandemic PeriodInterpandemic Period

EpidemicEpidemic

Time in YearsTime in Years11 22 33 44 55 66 77 88 99 1010 1111 1212

Incidence of clinically manifest influenzaIncidence of clinically manifest influenzaMean level of population antibody vs A HxNxMean level of population antibody vs A HxNxMean level of population antibody vs A HyNyMean level of population antibody vs A HyNy

Dünya Sağlık Örgütü Dünya Sağlık Örgütü Pandemi UyarısıPandemi Uyarısı

Epithelial demage()

No viremia Viral shedding5 -10 days

Onset of the symptoms(1-5 days)

Acute influenza Symptoms regress

(~ 5 day)Viral Pneumonia Sekonder Bakteriyel

Pnömoni/Komplikasyonlar

Common Diagnostic Common Diagnostic teststests

RapidRapid Antigen (EIA) Antigen (EIA)– Sensitivity: 60-80%Sensitivity: 60-80%– Specificity: 90%Specificity: 90%

CultureCulture (Shell Vial) (Shell Vial)– Sensitivity: 70-80% Sensitivity: 70-80% – Specificity: 100% Specificity: 100%

RT-PCR, multiplex RT, RT-PCR, multiplex RT, multiplex PCR, array, multiplex PCR, array, luminex basedluminex based

DFADFA

PARAMYXOVIRUSEPARAMYXOVIRUSESS

15 kb lineer, negative sense RNASpeherical to plemorphic r > 150 nm 6 structutal proteins

Unique Features of the Unique Features of the ParamyxoviridaeParamyxoviridae

Large virion consists of a negative RNA genome Large virion consists of a negative RNA genome in a helical nucleocapsid surrounded by an in a helical nucleocapsid surrounded by an envelope containing a viral attachment protein envelope containing a viral attachment protein (hemagglutinin-neuraminidase [HN], (hemagglutinin-neuraminidase [HN], parainfluenza virus and mumps virus; parainfluenza virus and mumps virus; hemagglutinin [H], measles virus; and hemagglutinin [H], measles virus; and glycoprotein [G], respiratory syncytial virus glycoprotein [G], respiratory syncytial virus [RSV]) and a fusion glycoprotein (F). [RSV]) and a fusion glycoprotein (F).

The three genera can be distinguished by the The three genera can be distinguished by the activities of the viral attachment protein: HN of activities of the viral attachment protein: HN of parainfluenza virus and mumps virus has parainfluenza virus and mumps virus has hemagglutinin and neuraminidase, and H of hemagglutinin and neuraminidase, and H of measles virus has hemagglutinin activity, but G measles virus has hemagglutinin activity, but G of RSV lacks these activities. of RSV lacks these activities.

Virus replicates in the cytoplasm. Virus replicates in the cytoplasm. Virions penetrate the cell by fusion with Virions penetrate the cell by fusion with

the plasma membrane and exit by the plasma membrane and exit by budding from the plasma membrane. budding from the plasma membrane.

Viruses induce cell-cell fusion, causing Viruses induce cell-cell fusion, causing multinucleated giant cells. multinucleated giant cells.

Paramyxoviridae are transmitted in Paramyxoviridae are transmitted in respiratory droplets and initiate respiratory droplets and initiate infection in the respiratory tract. infection in the respiratory tract.

Cell-mediated immunity causes many of Cell-mediated immunity causes many of the symptoms but is essential for the symptoms but is essential for control of the infection. control of the infection.

Measles virusMeasles virus

ParainfluenzavirusesParainfluenzaviruses

♦ PIV types 1 and 2 most often cause outbreaks of croup in autumn/early winter, with an alternate year pattern. PIV-1 tends to attack children ages 2-6 years.

♦ PIV-3 causes croup less commonly than PIV-1 and 2. Infections are sporadic and year-round, including spring and summer. Primary infection with PIV 3 in young infants and children <2 years of age is a fairly common cause of bronchiolitis and pneumonia.

♦ PIV-4 infections, even primary infections, are usually milder and are generally associated with mild URI symptoms.

♦ Particularly severe and persistent infections are known to occur in immunocompromised children and adults; prolonged viral shedding is seen.

Mumps virusMumps virus

Respiratory syncytial Respiratory syncytial virusvirus RSV ARSV A RSV BRSV B November-May epidemicsNovember-May epidemics

MetapneumovirusMetapneumovirus First described in 2001First described in 2001 Widespread; seropositivity among Widespread; seropositivity among

young adults and older people 100%young adults and older people 100% Smilar disaese as RSVSmilar disaese as RSV Between Decembre and AprilBetween Decembre and April Among young children less common Among young children less common

compared to RSVcompared to RSV

HenipavirusesHenipaviruses Hendra and Nipah virusesHendra and Nipah viruses Zoonotic viruses (fruit bats)Zoonotic viruses (fruit bats) Endemic – AustralasiaEndemic – Australasia Nipah virus Nipah virus Malaysia Malaysia

encephalitis (from pigs)encephalitis (from pigs) Hendra Hendra Australia (equine virus) Australia (equine virus)

Togaviridae and Togaviridae and FlaviviridaeFlaviviridae

RubellaRubella

TogaviridaeRubivirusPositive sense SS RNA70 nm9 genotypes

Incubation period: 12 days and longerViremia: Devopes after 7-9 days and lasts till appearence of rush but viral shedding continues20-50% subclinicalRush facetrunkextremities< 3 daysIn adults (esp. Women transient arthralgia)Rarely thrombocytopenic pupura and encephlaitisEpidemics every 6-10 yearsExplosive epidemics every 20-25 years

In first semester 85%In first semester 85%In second semester 15%In second semester 15%Intrauterine infection Intrauterine infection viral persistance viral persistance

positive-strand RNA positive-strand RNA 27–33 kb27–33 kb 3′ structural proteins, including 3′ structural proteins, including

spike (S), envelope (E), membrane spike (S), envelope (E), membrane (M) and nucleocapsid (N)(M) and nucleocapsid (N)

NS: replicase protein (ORF1 and 2)NS: replicase protein (ORF1 and 2)

Human CoronavirusHuman Coronavirus Group 1: Transmissible gastroenteritis virus Group 1: Transmissible gastroenteritis virus

(TGEV), porcine epidemic diarrhea virus (TGEV), porcine epidemic diarrhea virus (PDEV), feline infectious peritonitis virus (PDEV), feline infectious peritonitis virus (FIPV), canine coronavirus and (FIPV), canine coronavirus and HCoV-229E, HCoV-229E, HCoV-NL63HCoV-NL63

Group 2: Mouse hepatitis virus (MHV), bovine Group 2: Mouse hepatitis virus (MHV), bovine coronavirus, haemagglutinating coronavirus, haemagglutinating encephalomyelitis virus,encephalomyelitis virus, HCoV-HKU1 HCoV-HKU1 and and HCoV-OC43;HCoV-OC43; bat SARS-CoV and bat SARS-CoV and SARS-CoVSARS-CoV considered distantly related Group 2b considered distantly related Group 2b coronaviruses.coronaviruses.

Group 3: Avian coronavirusesGroup 3: Avian coronaviruses