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Orthomyxoviruses

Orthomyxoviridae

For medical students2 min readUpdated 2026-10-10

Orthomyxoviruses are a family of enveloped, negative-sense single-stranded RNA viruses. Their most medically significant representatives are influenza viruses, which cause acute respiratory infections accompanied by prominent systemic toxicity.

GenomeSegmented single-stranded RNA (negative-sense)

StructureEnveloped (complex) virions

EtymologyGreek *orthos* (straight) and *myxa* (mucus)

First isolationHuman influenza virus (type A) isolated in 1933

Classification and Taxonomy

The family Orthomyxoviridae derives its name from the Greek words orthos (meaning "straight") and myxa (meaning "mucus"). Structurally, they are enveloped viruses, meaning their nucleocapsid is surrounded by an outer lipoprotein envelope (supercapsid). Their genetic material consists of RNA.

The family comprises several notable genera that differ in host range and transmission routes:

Thogotovirus — tick-borne arboviruses.
Isavirus — includes pathogens affecting fish (specifically causing infectious salmon anemia).
Human pathogens are represented by three genera: Influenzavirus A, Influenzavirus B, and Influenzavirus C.

Features of Influenza A Virus

Among all family members, Influenzavirus A poses the greatest public health threat. This pathogen possesses three critical characteristics that make it a major focus for epidemiologists worldwide:

Anthropozoonotic potential. The virus can infect not only humans but also various animal species, creating a vast natural reservoir.
High antigenic variability. The pathogen constantly alters its surface structures, hindering the development of lasting, durable population immunity.
Epidemiological hazard. Due to this high variability and ability to cross species barriers, this virus type regularly causes large-scale epidemics.

Clinical Features of Influenza

Influenza is an acute viral respiratory illness. The etymology of terms designating this disease reflects its nature: the French word grippe means "to seize" or "to scratch," pointing to a sudden, sharp onset of symptoms. The historical term influenza originates from Italian, meaning "influence" of the stars or cold air.

The clinical presentation consists of a characteristic triad of manifestations:

Involvement of the respiratory tract tissues.
High fever accompanied by marked systemic toxicity.
Disruption of normal cardiovascular and nervous system functions.

History of Discovery and Isolation

Symptoms characteristic of influenza were documented long before the modern viral era. Descriptions of similar epidemics can be found in the works of Hippocrates and the Roman historian Livy.

The chronological isolation of influenza viruses is as follows:

1933 (Great Britain): Researchers W. Smith, C. Andrewes, and P. Laidlaw isolated the human influenza virus for the first time by inoculating ferrets with nasal washings from patients. This isolate was later classified as Type A.
1936 (USSR): Type A virus was successfully isolated by Soviet scientists — A.A. Smorodintsev in Leningrad and L.A. Zilber in Moscow.
1940: T. Francis and T. Magill discovered influenza B virus.
1947: R. Taylor first isolated influenza C virus.

Mnemonic

Influenza virus types were discovered in strict alphabetical order: A in 1933, B in 1940, and C in 1947.

Frequently asked questions

Which viral structures mediate adhesion and antigenic variation in influenza?

The surface glycoprotein hemagglutinin mediates viral binding to susceptible host cells. The major virion surface structures include:

Hemagglutinin (HA) — a trimer responsible for attachment and membrane fusion. The large HA1 subunit binds to host sialic acid receptors.
Neuraminidase (NA) — a tetramer that cleaves sialic acid residues to facilitate viral release and penetration through endocytosis.

Influenza A displays notable antigenic diversity driven by antigenic drift and shift.

What are the main steps of the influenza replication cycle in a host cell?

The replication cycle takes approximately 5–6 hours and proceeds through sequential stages:

Adsorption — binding of hemagglutinin to cell-surface sialic acid receptors.
Penetration — entry via receptor-mediated endocytosis, facilitated by NA activity.
Uncoating — release of the viral genome into the cytoplasm.
Transcription and Replication — unlike most RNA viruses, influenza replication and transcription occur in the nucleus.
Assembly — packaging of viral genomic segments and structural proteins.
Budding and Release — viral progeny exit the cell, aided by neuraminidase, which prevents virion aggregation.

Which genera of orthomyxoviruses cause human disease?

Human pathogens belong to three genera: Influenzavirus A, Influenzavirus B, and Influenzavirus C.

Why is influenza A virus considered the most dangerous?

It exhibits significant antigenic variability and can infect both humans and animals (zoonotic reservoir), driving its high epidemiological risk.

What comprises the clinical triad of influenza?

The triad includes respiratory tract involvement, fever with systemic toxicity, and neurological/cardiovascular dysfunction.

Go deeper

Mechanisms of antigenic drift and shift in Influenza A
Structure and function of the orthomyxovirus envelope
Intracellular replication cycle of influenza virus
Pathogenesis of systemic toxicity and fever in influenza