Taxonomy and virion structure
The family Bunyaviridae includes over 250 serotypes. Pathogenic to humans are four genera: Orthobunyavirus, Phlebovirus, Nairovirus, and Hantavirus. The prototype of the entire family is considered to be the Bunyamwera virus, isolated in Uganda from mosquitoes.
Morphologically, they are complex enveloped viruses of spherical or oval shape. Under electron microscopy, they resemble a "doughnut".
Genome and core structure: The genome is represented by negative-sense RNA, which is fragmented into three segments. By size, they are divided into:
- L (long) — large segment;
- M (medium) — medium segment;
- S (short) — small segment.
Each RNA fragment is associated with the nucleocapsid protein N, forming three independent ribonucleocapsids with helical symmetry. The core also contains the enzyme transcriptase — RNA-dependent RNA polymerase (encoded by the L-segment).
Envelope and surface antigens: The core is surrounded by a lipoprotein envelope (supercapsid). On its surface are spikes consisting of glycoproteins Gn and Gc (encoded by the M-segment).
- Glycoproteins are responsible for organotropism (tissue affinity), hemagglutinating properties, and transmission efficiency via vectors. These are type-specific antigens detected in neutralization tests (NT) and hemagglutination inhibition tests (HIT).
- The internal protein N carries group-specific properties and is detected in the complement fixation test (CFT).
Reproduction features
The life cycle of bunyaviruses proceeds exclusively in the cytoplasm of the host cell. The synthesis of viral structures occurs very rapidly: the nucleocapsid protein N can be detected in the cell as early as 2 hours after infection.
The main feature of the family is the assembly mechanism of new virions. Viral particles are formed by budding, not through the outer plasma membrane of the cell, but through the smooth membranes of the Golgi apparatus. Then the formed virions are packaged into vesicles, transported to the plasmalemma, and leave the cell predominantly via exocytosis. Virus release via cell lysis occurs rarely.
Epidemiology and ecological groups
Bunyaviruses are distributed globally. They cause naturally focal zoonotic infections. According to their mechanism of circulation in nature, they are divided into two large ecological groups:
- Arboviruses (transmitted by arthropods).
They include the majority of bunyavirus genera. Arthropods serve not only as vectors but also as the primary natural reservoir. The virus is adapted to two temperature regimes: 36–40 °C (warm-blooded hosts) and 22–25 °C (arthropods). In the vector population, the virus is maintained through transovarial (through eggs to offspring) and transphasic (from larva to imago) transmission.
- Orthobunyavirus (California encephalitis virus) — vectors are mosquitoes.
- Phlebovirus (sandfly fevers, Rift Valley fever viruses) — sandflies and mosquitoes.
- Nairovirus (Crimean-Congo hemorrhagic fever virus) — predominantly ixodid ticks (the main vectors in the territory of the Russian Federation).
- Roboviruses (transmitted by rodents).
This group includes only the genus Hantavirus (causative agents of hemorrhagic fever with renal syndrome — Hantaan, Puumala viruses, etc.). They lack an arthropod vector. The evolution of hantaviruses is strictly linked to specific rodent species (co-evolution process). Unlike other genera, disordered granular-filamentous structures are present inside the hantavirus virion.
Human transmission mechanisms: vector-borne (bite) or contact (contact of infected animal/human secretions with damaged skin and mucous membranes).
Resistance, cultivation, and diagnosis
Due to the presence of a lipid envelope, bunyaviruses are sensitive to fat solvents (ether, detergents) and standard disinfectants. They are stable only within a narrow pH range (6.0–9.0). Viruses are thermolabile: inactivated at 56 °C for 30 minutes, and instantly upon boiling. However, they retain infectivity remarkably well during prolonged freezing.
Since these viruses are causative agents of particularly dangerous infections (PDIs), work with them is permitted only in high-containment laboratories.
Cultivation methods:
- In vivo: the universal model is newborn white mice. Intracerebral (into the brain) inoculation causes fatal encephalitis in them.
- In vitro: cell cultures (human embryonic kidney, BHK-21, chicken embryo fibroblasts, Vero E-6 cells for hantaviruses). Feature: the cytopathic effect (CPE) is weakly expressed, therefore the immunofluorescence assay (IFA) must be used for virus detection in culture.
Briefly: answers to topical questions
What clinical syndromes are caused by viruses of the genus *Hantavirus* in humans?
Viruses of the genus Hantavirus cause two main clinical syndromes in humans. The first is hemorrhagic fever with renal syndrome, caused by Hantaan, Puumala, Seoul, Dobrava, and Amur viruses. The second is hantavirus cardiopulmonary syndrome, associated with Sin-Nombre, Black Creek, New York, Bayou, Andes, and Laguna Negra viruses.
- Hemorrhagic fever with renal syndrome is a clinical form caused by Puumala, Seoul, Amur, Hantaan, and Dobrava viruses.
- Hantavirus cardiopulmonary syndrome is a syndrome first described in the USA in 1993, caused by Sin-Nombre, Black Creek, New York, Bayou, Andes, and Laguna Negra viruses.
What are the mechanisms and routes of human hantavirus infection?
Hantaviruses are roboviruses: rodents are their primary hosts, and there is no vector. In rodents, virus transmission occurs predominantly via the airborne route. The virus is released into the environment with feces, urine, and saliva.
Which target cells are primarily affected in the human body upon bunyavirus infection?
During hantavirus infection, target cells include endotheliocytes, macrophages, platelets, and renal tubular epithelial cells. Virus penetration is due to the presence of specific integrin receptors of various classes on the membranes of target cells.
Bunyaviruses have a 3-part genome: L, M, S. Remember it like clothing sizes (Large, Medium, Small). And they bud as if "getting dressed" — through the Golgi apparatus rather than the cell membrane.
Class and exam questions
Which method is primary for biological virus isolation?
Intracerebral inoculation of newborn white mice, as they are most susceptible to the infection.
How can a virus be detected in cell culture if it does not cause cell destruction?
Due to the weak cytopathic effect, the immunofluorescence assay (IFA) is used to detect bunyaviruses in cell cultures.
What else to study on this topic
- Clinical manifestations and pathogenesis of hemorrhagic fever with renal syndrome (HFRS).
- Specific diagnosis of Crimean-Congo hemorrhagic fever (CCHF).
- Molecular genetic methods for detecting viral RNA (PCR).
- Methods of bunyavirus inactivation and development of killed vaccines.
- Use of antiviral drugs (ribavirin) in severe cases of infection.
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