Last Updated on September 6, 2020 by Sagar Aryal

Source: Viral Zone

The ribonucleocapsid is filamentous and 200-300nm long, depending on the arrangement, and 2-2.5 nm wide.

The capsid or nucleocapsid is elongated with helical symmetry.

These projections are 5-10 nm long and they produce a grid-like structure.

Surface projections are distinctive spikes which are surrounded by a prominent fringe embedded in a lipid bilayer that is 5 nm thick.

The envelope surrounds three nucleocapsids and has surface projections.

The virus capsid is enveloped by a single layer envelope.

The virion displays round or pleomorphic morphology with a diameter of roughly 120-160 nm.

Source: Viral Zone

The genome segments, encapsidated by the N protein to form ribonucleoproteins, are enclosed inside a lipid envelope that is decorated by spikes composed of Gn and Gc.

Some hantaviruses also encode a NSs protein on their S segment.

The segments, respectively, encode three structural proteins: nucleocapsid (N) protein, two glycoproteins Gn and Gc and an RNA-dependent RNA-polymerase.

L segment is between 6.8 and 12 kb, M segment between 3.2 and 4.9 kb and S segment between 1 and 3 kb.

The single-stranded, negative-sense, RNA genome of hantavirus is trisegmented into small, medium and large (S, M, and L) segments.

Figure: Geographical representation of approximate incidence of hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) by country per year (data update to 2016). Source: https://doi.org/10.1007/s12250-016-3899-x

The vast majority of HPS and HFRS infections are not transferred from person to person.

Like HPS, HFRS results from hantaviruses that are transmitted by rodent urine, droppings, or saliva (rodent bite), by direct contact with the animals, or by aerosolized dust contaminated with rodent urine or feces to human skin breaks or to mucous membranes of the mouth, nose, or eyes.

HPS is found mainly in the Americas (Canada, U.S., Argentina, Brazil, Chile, Panama, and others) while HFRS is found mainly in Russia, China, and Korea but may be found in Scandinavia and Western Europe and occasionally in other areas.

Hantavirus are carried by rodents and can cause severe respiratory infections termed hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS).

The 2012 outbreak at Yosemite National Park was due to hantavirus transfer to humans by deer mice.

Hantavirus was first identified in an outbreak in 1993 in the “Four Corners” area of the southwestern U.S. and found to be transmitted to humans by rodent urine, feces, saliva, and by airborne particles containing these items.

Source: DOI: 10.1128/CMR.00062-09

The ribonucleocapsids buds at the Golgi apparatus, releasing the virion by exocytosis.

Replication presumably starts when enough nucleoprotein is present to encapsidate neo-synthetized antigenomes and genomes.

Viral mRNAs are capped in the cytoplasm.

The RNA dependent RNA polymerase (RdRp) complex initiates transcription by binding to the leader sequence in 3′ of the genomic negative-strand RNA.

The fusion of virus membrane with the vesicle membrane results in the release of ribonucleocapsid segments in the cytoplasm.

Endocytosis can occur via clathrin-mediated endocytosis, caveolin-mediated endocytosis or clathrin- and caveolin-independent endocytosis.

The virus attaches to host receptors though Gn-Gc glycoprotein dimer, and is endocytosed into vesicles in the host cell.

Source: https://doi.org/10.3389/fmicb.2014.00727

Humans are infected by hantavirus mainly through inhalation of aerosolized virus-contaminated rodent excreta and the higher the number of infected rodents, the higher the risk of human infection.

Hantaviruses cause two potentially lethal diseases, HPS and HFRS, and both diseases result in defects in vascular permeability and platelet function.

Human beta 3 integrins confer cellular susceptibility to HPS- and HFRS-causing hantaviruses, a fact directly linking platelets, endothelial cells, and hantavirus diseases to the use of cellular receptors that maintain capillary integrity and regulate platelet function.

The incubation period of hantavirus is relatively long: 2‒4 weeks.

The very first barrier that the virus encounters when entering the body is the mucus gel that covers respiratory epithelial cells.

In the lower respiratory tract, trapped microbes are removed by the ciliated cells that continually move the mucus with their cilia―away from the lungs to the throat.

When the virus has passed the mucus gel, it encounters yet another barrier―the respiratory epithelium which has tight junction integrity and forms a particle-impermeable barrier and affects club cells.

Despite being infected, these cells show no cytopathic effect (CPE) and the epithelial tight junction integrity is intact.

The virus is able to infect via both the apical membrane and the basolateral membrane, and subsequently, virus particles are secreted bidirectionally.

Once the respiratory epithelium has been traversed, the virus spreads to the lung endothelium and more distant locations in the body.

Hantaviruses causing HFRS have tropism for cells in the kidneys, and they are found in podocytes in the glomeruli and in tubular epithelial cells of infected patients.

In HCPS(Hantavirus Cardio Pulmonary Syndrome) patients, the virus can also be found in tubular epithelial cells but usually to a low degree.

Studies on biopsy specimens showed inflammatory cellular infiltration close to infected lung endothelial cells in HCPS patients and close to infected kidney cells in HFRS patients.

The infiltrations of inflammatory cells in the kidneys of HFRS patients included lymphocytes (mainly CD8+ T-cells), monocytes, macrophages, and polymorphonuclear leukocytes (including eosinophilic granulocytes and neutrophils).

Kidney biopsy samples from HFRS patients have shown increased expression of cytokines (TNF-α, TGF-β, and PDGF) in the peritubular areas.

Elevated serum levels of TNF-α is observed in both HCPS patients and HFRS patients.

TNF-α is a pro-inflammatory cytokine that causes increased vascular permeability.

Very high serum levels of IL-6 is found in fatal cases of HCPS.

Elevated levels of IFN-γ, IL-12, and TNF-β in HCPS patients indicate an elevated Th1 response.

The Th1 response plays a key role in antiviral immunity, but it can also produce an immunopathogenic effect.

Infection of endothelial cells induces the production of chemokines, which attract immune cells.