OrthomyxoviridaeEdit
Orthomyxoviridae is a family of enveloped, segmented, negative-sense RNA viruses that are best known for causing influenza in humans, birds, and a wide range of mammals. These viruses are notable for their genetic flexibility, courtesy of a segmented genome that permits reassortment when multiple strains co-infect a host. The result is continual antigenic variation and, on occasion, sudden emergences of new strains with pandemic potential. The most familiar members affecting humans are influenza A virus and influenza B virus, though influenza C virus and influenza D virus play roles in animal and, less commonly, human infections as well. Orthomyxoviridae Influenza A virus Influenza B virus Influenza C virus Influenza D virus
Taxonomy and genome organization
Orthomyxoviridae comprises several genera, with Influenzavirus A, Influenzavirus B, Influenzavirus C, and Influenzavirus D representing the lines most relevant to vertebrate hosts. A and B are the principal human pathogens responsible for seasonal flu outbreaks; C and D more commonly infect animals and occasionally humans. The viruses share a common architecture: an enveloped virion displaying surface glycoproteins that mediate cell entry and release, and a segmented genome that encodes the viral polymerase and structural proteins. In influenza A and B, the surface proteins are separate hemagglutinin (HA) and neuraminidase (NA) glycoproteins; influenza C and influenza D use a single surface glycoprotein called HEF (hemagglutinin-esterase-fusion), which performs the roles of both receptor binding and fusion. This distinction has implications for antigenicity and immune recognition. Hemagglutinin Neuraminidase HEF
The genome of orthomyxoviruses is segmented and negative-sense RNA. The number of segments varies by genus, generally seven or eight, and encoding a set of proteins including the polymerase complex (PB2, PB1, PA), nucleoprotein (NP), matrix proteins (M1/M2), nonstructural proteins (NS1/NEP), and the surface glycoproteins (HA or HEF and NA or NA-like). The segmented nature of the genome is central to how these viruses evolve: during co-infection of a cell with distinct strains, genome segments can reassort, producing offspring with novel antigenic constellations. PB2 PB1 PA NP M1 M2 NS1 NEP HA HEF NA
Life cycle and replication
Orthomyxoviruses initiate infection by attaching to sialic acid receptors on respiratory tract cells, with receptor preference influencing host range and tissue tropism. After entry, the viral ribonucleoprotein complexes are transported to the nucleus, where transcription and replication occur—a distinctive feature among RNA viruses. The viral polymerase complex carries out transcription via cap-snatching from host pre-mRNAs, enabling efficient synthesis of viral mRNAs. Translation of these messages yields structural and regulatory proteins, which assemble with replicated genome segments and emerge as progeny virions through budding, aided by HA/HEF and NA or their equivalents to mediate attachment and release. Cap-snatching Ribonucleoprotein complex Host transcription Hemagglutinin HEF Neuraminidase
Reassortment during coinfection can create antigenically shifted strains with altered HA/NA combinations, potentially evading preexisting immunity in the population. Antigenic drift—accumulation of point mutations in surface proteins—also continuously reshapes antigenicity and contributes to seasonal illness. These evolutionary dynamics underlie the need for ongoing surveillance and periodic updates to vaccine composition. Antigenic shift Antigenic drift Reassortment Surveillance (epidemiology) Vaccine strain selection
Hosts, transmission, and disease
Humans primarily experience influenza A and B infections, with symptoms ranging from fever and muscle aches to cough, malaise, and respiratory distress. Disease severity depends on factors such as age, immune status, and viral virulence. Birds, swine, horses, and a broad array of mammals can harbor orthomyxoviruses, making animals an important reservoir and source of novel strains. Transmission occurs via respiratory droplets and, in some settings, aerosols, with environmental and seasonal factors shaping outbreak patterns in temperate and tropical regions. Influenza Pandemic Zoonosis Avian influenza
Diagnosis, treatment, and prevention
Clinical diagnosis is supported by laboratory testing, including rapid antigen assays, RT-PCR assays targeting segment sequences, and viral culture in specialized laboratories. Molecular methods are preferred for their sensitivity and ability to distinguish among A, B, C, and D lineages and to identify specific strains. RT-PCR Viral culture Influenza testing
Treatment combines supportive care with antiviral agents. Neuraminidase inhibitors (such as oseltamivir and zanamivir) reduce viral spread and lessen disease severity when given early in the course of illness. Baloxavir marboxil, a polymerase acidic endonuclease inhibitor, represents another therapeutic option with a distinct mechanism. Resistance can emerge, highlighting the need for prudent use and ongoing drug development. Vaccination remains the cornerstone of prevention. Seasonal vaccines are formulated to match circulating strains and are delivered as inactivated or live-attenuated preparations, with ongoing advances in cell-based and recombinant approaches. Public health measures, surveillance, and rapid response to novel strains are essential components of reducing the burden of disease. Oseltamivir Zanamivir Baloxavir marboxil Vaccine Recombinant vaccine Cell-based vaccine Surveillance (epidemiology) Influenza vaccine strain selection
Research and controversies
The study of orthomyxoviruses intersects virology, immunology, and public health policy. Key debates center on the best strategies for vaccine design, strain matching, and the balance between broad, universal protection and annual customization. Some stakeholders advocate for broader vaccination programs and accelerated development of universal vaccines to reduce the need for frequent reformulation, while others emphasize individual choice and the costs and logistics of public health campaigns. Regardless of perspective, the science emphasizes the importance of surveillance, transparency in reporting, and investment in antiviral options and rapid diagnostics to mitigate outbreaks. Universal vaccine Vaccine development Public health policy
See also discussions of antigenic variation, viral replication in the nucleus, and mechanisms of host adaptation, all of which shape the ongoing response to orthomyxoviruses. Antigenic variation Nucleus (cellular biology) Host adaptation