Human Influenza Virus Overview

Overview of Human Influenza Virus

• Human influenza virus is a helical enveloped virus
• It contains negative-sense, single-stranded RNA
• It belongs to the Orthomyxoviridae family

Influenza Virus Types

• Influenza A causes worldwide epidemics and pandemics
• Influenza B causes major outbreaks
• Influenza C causes mild respiratory infections, not outbreaks
• Influenza viruses are the only members of the Orthomyxoviridae family
• Virions are pleomorphic, appearing spherical or tubular

Structure of Influenza Virus

• Composed of a segmented, single-stranded RNA genome
• Features a helical nucleocapsid
• Has an outer lipoprotein envelope
• The envelope has hemagglutinin (HA) and neuraminidase (NA) spikes

Hemagglutinin and Neuraminidase Subtypes

• Influenza A has 16 antigenically distinct HA types
• Influenza A has 9 antigenically distinct NA types
• Influenza viruses, especially A, change the antigenicity of HA and NA proteins, contributing to epidemics and pandemics

Antigenic Changes

• Antigenic shift is a major change based on reassortment of genome RNA segments
• Antigenic drift is a minor change based on mutations in the genome RNA

Epidemiology

• Transmitted via airborne respiratory droplets
• Antigenic shift variants appear infrequently in influenza A
• Antigenic drift variants appear virtually every year in influenza A
• The last major antigenic shift causing a human pandemic was in 1968 with H3N2 emergence
• Influenza B undergoes antigenic drift but not shift
• Antigenic changes in influenza B are less dramatic and frequent than in influenza A
• Occurs primarily in the winter (December to February) in the Northern Hemisphere
• Influenza, followed by bacterial pneumonia, causes significant mortality, especially in older people
• Morbidity from influenza is higher in older people and children under two years

Pathogenesis

• Neuraminidase clears the protective mucous layer, allowing virus access to respiratory tract cells
• Initially establishes a local upper respiratory tract infection
• The virus targets and kills mucus-secreting, ciliated, and other epithelial cells, leading to loss of the primary defense system
• Lack of ciliated epithelium means swallowed oral and nasal bacteria (e.g., Streptococcus pneumoniae) cannot be expelled, possibly leading to pneumonia
• Infection promotes bacterial adhesion to epithelial cells
• Pneumonia may result from viral pathogenesis or secondary bacterial infection
• Influenza infection is an excellent inducer of interferons
• Systemic interferon and cytokine responses peak at 3-4 days post-infection, coinciding with viral shedding
• These responses cause systemic flu-like symptoms
• Infection depresses macrophage and T-cell function
• Protection against reinfection is primarily associated with antibodies to hemagglutinin, but antibodies to neuraminidase are also protective

Clinical Symptoms

• After a 24-48 hour incubation, symptoms develop suddenly: fever, myalgias (muscle pain), headache, sore throat, cough
• Severe myalgias coupled with respiratory symptoms are typical
• Vomiting and diarrhea are rare
• Symptoms usually resolve spontaneously in 4-7 days, but influenza or bacterial pneumonia can complicate the course
• Pneumonia caused by Staphylococcus aureus or Streptococcus pneumoniae is a known complication
• Reye's syndrome, characterized by encephalopathy and liver degeneration, is a rare but life-threatening complication in children following some viral infections, particularly influenza B and chickenpox

Diagnosis

• Diagnoses are mostly made on clinical grounds, but lab tests are available
• ELISA is the most commonly used test.
• Rapid tests for physician's offices include Flu Optical Immunoassay and FluQ Influenza Test which detects viral antigen using monoclonal antibodies
• The G STAT Flu Test detects viral neuraminidase
• Direct fluorescent antibody (DFA) testing and PCR are also used

Treatment and Prevention

• Oseltamivir (oral) and Zanamivir (inhaled) are commonly used treatments
• Peramivir (IV) is also available
• These drugs are neuraminidase inhibitors, which inhibit the release of the virus from cells
• Effective against both influenza A and B viruses

Prevention of Influenza

• Inactivated vaccine is recommended for adults
• Live attenuated vaccine is recommended for children
• Live vaccines should NOT be given to pregnant women or immunocompromised individuals
• Both vaccines are made in chicken eggs, which isn't suitable for individuals with egg allergies