Viral Infections of the Respiratory System

 Common cold (rhinitis)  Pharyngitis  Tonsilitis  Sinusitis & otitis media  Croup (acute laryngotracheobronchitis)  Acute bronchitis  Acute bronchiolitis  Viral pneumonia  Influenza (Flu) Clinical manifestations

Name of the virus FamilyDisease 1- Influenza virusOrthomyxoviridaeURT & LRT infection 2- Parainfluenza virusParamyxoviridaeURT & LRT infection 3- Respiratory syncytial virusParamyxoviridaeLRT infection 4- RhinovirusPicornaviridaeURT infection 5- CoronavirousCoronaviridaeURT infection 6- AdenovirusAdenoviridaeURT and eye infections 7- Human metapneumovirusParamyxoviridaeLRT infection The common respiratory viruses  Upper respiratory tract infection includes  rhinitis (common cold), tonsillitis, pharyngitis  Lower respiratory tract infection includes  croup, bronchitis, bronchiolitis, pneumonia

ORTHOMYXOVIRIDAE  Orthomyxoviruses are spherical, enveloped viruses containing a segmented, negative strand RNA genome  Viruses in this family infect humans, horses, and pigs, and are the cause of influenza  Orthomyxoviruses are divided into three types:  Influenzae A, B, and C  Only influenza virus types A and B are of medical importance  Type A influenza viruses differ from type B viruses in that they have an animal reservoir and are divided into subtypes  Influenza virus C is not a significant human pathogen

Structure  Influenza virions are spherical, enveloped, pleomorphic particles  Two types of spikes project from the surface  One is composed of H protein and the second of N protein  Both the H and N influenza proteins are integral membrane proteins  The M (matrix) proteins underlie the viral lipid membrane  The RNA genome, located in a helical nucleocapsid, is composed of eight distinct segments of RNA  Each of which encodes one or more viral proteins  Each nucleocapsid segment contains not only the viral RNA but also four proteins

Influenza Virus  Orthomxoviridae family  They are helical, enveloped, single stranded RNA genome  They are enclosed in a lipid envelop and a layer of glycoprotein spikes  known as haemagglutinin (HA) and neuraminidase (NA), which are major antigenic determinants  They are divided into different genera on the basis of the nucleoprotein antigen  Genera A, B, C  Pathogenesis  The virus infects the epithelial cells of the nose, throat, bronchi and occasionally the lungs

Clinical Significance  Influenza spread by respiratory droplets and is an infection solely of the respiratory tract  There is rarely viremia or spread to other organ systems  Influenza has an acute onset, with symptoms including a nonproductive cough and chills, followed by high fever, muscle aches, and extreme drowsiness  Runny nose is unusual, differentiating influenza virus infection from the common cold  The disease runs its course in 4 to 5 days, after which recovery is gradual  The most serious problems, such as development of pneumonia or bacterial pneumonia

Influenza Virus Electron micrograph.

Influenza viral proteins  Haemagglutinin (H)  Attachment to the cell surface receptors  Antibodies to the HA is responsible for immunity  16 haemagglutinin antigenic type, H1 – H16  Human associated H antigenic type are H1, H2, H3  Neuraminidase (N)  Responsible for release of the progeny viral particles from the infected cell  9 neuraminidase antigenic type, N1 – N9  Human associated N antigenic type are N1, N2

Summary of the ecology of influenza viruses

 Prevention  Influenza vaccine: Two types of vaccines available 1- The flu shot vaccine: Inactivated (killed vaccine)  Given to people older than 6-months, including healthy people and those with chronic medical conditions 2- The nasal spray flue vaccine: Live attenuated vaccine  Approved for use in healthy people between 5-49 years of age  Both vaccines contain two strains of the current circulating influenza A and B viruses  Vaccine should be given in October or November  before the influenza season begins

Role of H AND N Proteins H = Hemagglutinin and N = Neuraminidase Hemagglutinin allows the virus to bind to host cells Neuraminidase helps the virus to release itself from the highjacked cells in which it has reproduced Influenza A Virus Constantly Changes  Antigenic drift  Small changes in H or N proteins that occur from year to year  Population is partially immune, but may be re-infected over time (periodic epidemics)  Antigenic shift  Acquisition of new H or N protein, possibly from an animal virus  Population is not immune, everyone is susceptible (pandemics)

Influenza A Virus Influenza A virus only is further classified into subtypes based upon HA and NA antigens 16 HA subtypes and 9 NA subtypes are now recognized circulating in birds, humans, swine and horses The most famous subtypes are: A (H1N1): circulating in humans causing swine flu A (H5N1): circulating in birds causing avian flu

Clinical picture Fever Headache Myalgia Cough Rhinitis Ocular Symptoms Incubation period: 1 to 2 days Transmission: droplet infection or hand-to-hand contact Diagnosis: 1- Isolation of the virus from nose, throat swab 2- Tissue culture 3- Provisional - clinical picture + outbreak

Avian flu Viral etiology: Avian influenza type A virus (H5N1) Family: orthomyxovirus Epidemiology Wild birds are the natural reservoir for the virus They shed the virus in saliva, nasal secretion and feces All domestic poultry are susceptible to infection They become infected, when they eat food contaminated with secretion from infected bird Avian influenza viruses do not usually infect human High risk group includes those who working in poultry farms and those who are in close contact with poultry

 Symptoms in human  Ranges from typical flu to severe acute respiratory disease  Diarrhea, abdominal pain and bleeding from the nose have been reported  Treatment  Should be initiated within 48 hours  Lab diagnosis  PCR, detection of the viral RNA in throat swap

 Family: Paramyxoviridae  Structural features  Enveloped virus with - ssRNA genome, with 5 serotypes  Transmission  Inhalation of infectious aerosol droplets mainly in winter  Clinical syndrome a.Croup (or laryngotracheobronchitis) b.Fever, harsh cough, difficult inspiration can lead to airway obstruction need hospitalization to do tracheostomy c.Bronchiolitis and Pneumonia Lab diagnosis Direct detection immunofluorescence Treatment and prevention Supportive treatment, No specific treatment or vaccine available Parainfluenza Virus

Respiratory Syncytial Virus (RSV)  Family: Paramyxoviridae  Structural features: Enveloped virus with - ssRNA genome  Transmission: Inhalation of infectious aerosols mainly in winter  Clinical syndromes: a.Bronchiolitis a.Life-threatening disease in infant especially under 6 month of life with respiratory distress and cyanosis can be fatal and can lead to chronic lung disease in later life b.Pneumonia a.can also be fatal in infant

 Lab diagnosis  Isolated of virus by cell culture  Direct detection of the Ag by direct I.F.  Treatment and prevention  Ribavirin administered by inhalation for infants with severe cases  Vaccine  No vaccine available, but passive immunization immunoglobulin can be given for infected premature infants

Rhinovirus  Family: Picornaviridae  Structural features: Non-enveloped virus with + ssRNA genome, more than 100 serotypes available  Transmission: Inhalation of infectious aerosol droplets  Clinical symptoms: The 1 st cause of common cold. The main symptoms of common cold are sneezing, clear watery, nasal discharge with mild sore throat, and cough  Lab diagnosis: Direct detection of the Ag by direct I.F.  Treatment and prevention: Usually self-limiting disease, no specific treatment, and no vaccine available

Coronavirus  Family: Coronaviridae Structural features: They are large helical, enveloped, single stranded RNA viruses  Transmission: Inhalation of infectious aerosol droplets  Clinical symptoms: The 2 nd cause of common cold. The human coronaviruses (CoVs) are responsible for about 30% of mild upper respiratory tract illness (common cold) Severe Acute Respiratory Syndrome (SARS) Newly emerged SARS-CoV causes severe acute respiratory syndrome (SARS) that has been reported in Asia, North America, and Europe  In winter of 2002, a new respiratory disease known as (SARS) emerged in China  A new mutation of coronavirus MERS-CoV, with probably an animal reservoir, and cause atypical pneumonia with difficulty in breathing  Treatment and prevention: No specific treatment or vaccine available, yet

SARS Disease Severe acute respiratory syndrome (SARS) viral respiratory disease zoonotic origin caused by the SARS coronavirus (SARS-CoV) Incubation period: days Transmission: droplet infection or contact to contaminated skin or fomites Clinical Picture Fever, chills, headache, myalgia and malaise Respiratory symptoms often begin 3-7 days after symptom onset and peak in the second week Laboratory Diagnosis  Serological Testing  IFA: Indirect fluorescent antibody  ELISA: Enzyme-linked immunosorbent assays  Molecular Testing  RT-PCR: Reverse transcriptase-PCR  Culture: SARS-CoV (Vero E6 cell)

Adenovirus  Family: Adenoviridae  Structural features: Non-enveloped virus with ds-DNA genome  Pathogenesis: Adenovirus infects epithelial cell lining respiratory tract, conjunctiva, urinary tract, gastrointestinal tract and genital tract.  Clinical syndrome 1.Phrayngitis and tonsilitis 2.Pharyngioconjunctivitis 3.Keratoconjunctivitis 4.Pneumonia: in preschool children 5.Gastroenteritis 6.Acute hemorrhagic cystitis 7.Cervicitis and urethritis  Treatment and prevention: No specific treatment or vaccine