Hantavirus infection pathophysiology
|
Hantavirus infection Microchapters |
|
Patient Information |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Hantavirus infection pathophysiology On the Web |
|
American Roentgen Ray Society Images of Hantavirus infection pathophysiology |
|
Directions to Hospitals Treating Hantavirus pulmonary syndrome |
|
Risk calculators and risk factors for Hantavirus infection pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]
Overview
Hantavirus is usually transmitted via the inhalation of aerosolized viral antigens or rodent bites. The incubation period of hantavirus infection is of 9 to 33 days. Following inhalation, the virus replicates in pulmonary macrophages and dendritic cells. The primary target cells of hantavirus infection are endothelial cells of capillaries. Infection is followed by impairment of the barrier function of endothelial cells, fluid extravasation, and subsequent organ failure.
Pathophysiology
Reservoir
Each Hantavirus species is associated with a specific rodent in a given geographic region. Rodent subfamilies associated with hantaviruses include
- Arvicolinae (Europe)
- Murinae (Europe and Asia)
- Sigmodontinae (Americas)
Transmission
Hantavirus is usually transmitted via the inhalation of aerosolized viral antigens or rodent bites. Human to human transmission is seen in American Hantaviruses species (Andes virus).
Incubation period
The incubation period of hantavirus infection is of 9 to 33 days.[1]
Seeding
Following inhalation, the virus replicates in pulmonary macrophages and dendritic cells.
Pathogenesis
The pathogenesis of hantavirus infection can be described by impairment of the barrier function of endothelial cells, fluid extravasation and subsequent organ failure.[2]
Impairment of the barrier function of endothelial cells
- The primary target cells of hantavirus infection are endothelial cells of capillaries. Most commonly endothelial cells of lungs and heart are involved.
- Hantaviruses attach to beta-3 integrin receptors of endothelial cells and stimulate T cells.[3][4]
- Neutralizing antibody (NAbs) are produced as a result of stimulation and beta-3 integrins are inactivated.
- Inactivation of virus-bound beta-3-integrins contributes to deregulation of vascular endothelial growth factor receptor-2 (VEGFR2) and diminished antagonism of vascular endothelial growth factor (VEGFA).[5]
- This leads to impairment of vascular endothelial (VE) cadherin expression and subsequent loss of endothelial barrier function.
- Platelets are consumed in high number in response to the damage to the endothelial layer resulting in thrombocytopenia.
Fluid extravasation
- Neutralizing antibody (NAbs) also inhibit innate type I interferon (IFN) responses of endothelial cells.
- This results in inhibition of upregulation of CD73 by IFN-beta on endothelial cells and promotes vascular leakage.
Multiorgan failure
- Hantaviruses demonstrated to have an immunoreceptor tyrosine-based activation motif (ITAM) on their G1 envelope glycoproteins.
- Immunoreceptor tyrosine-based activation motif along with local T-cell cytokine production results in cellular downstream and immune cell dysfunction.[6]
- Attachment of hantavirus to beta-2 integrin receptors on neutrophils also induces the release of neutrophil extracellular traps.
- Sensitized mononuclear cells infiltrate the lung, myocardial interstitium, and spleen to produce cytokines, particularly TNF-alpha and interferon-gamma, resulting in pulmonary edema and myocarditis
References
- ↑ "Incubation Period of Hantavirus Cardiopulmonary Syndrome - Volume 12, Number 8—August 2006 - Emerging Infectious Disease journal - CDC".
- ↑ Spiropoulou CF, Srikiatkhachorn A (2013). "The role of endothelial activation in dengue hemorrhagic fever and hantavirus pulmonary syndrome". Virulence. 4 (6): 525–36. doi:10.4161/viru.25569. PMC 5359750. PMID 23841977.
- ↑ Gavrilovskaya IN, Shepley M, Shaw R, Ginsberg MH, Mackow ER (1998). "beta3 Integrins mediate the cellular entry of hantaviruses that cause respiratory failure". Proc. Natl. Acad. Sci. U.S.A. 95 (12): 7074–9. PMC 22743. PMID 9618541.
- ↑ Gavrilovskaya IN, Peresleni T, Geimonen E, Mackow ER (2002). "Pathogenic hantaviruses selectively inhibit beta3 integrin directed endothelial cell migration". Arch. Virol. 147 (10): 1913–31. doi:10.1007/s00705-002-0852-0. PMID 12376753.
- ↑ Geimonen E, Neff S, Raymond T, Kocer SS, Gavrilovskaya IN, Mackow ER (2002). "Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses". Proc. Natl. Acad. Sci. U.S.A. 99 (21): 13837–42. doi:10.1073/pnas.192298899. PMC 129784. PMID 12368479.
- ↑ Mori M, Rothman AL, Kurane I, Montoya JM, Nolte KB, Norman JE, Waite DC, Koster FT, Ennis FA (1999). "High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome". J. Infect. Dis. 179 (2): 295–302. doi:10.1086/314597. PMID 9878011.