West nile virus infection pathophysiology

Jump to navigation Jump to search

West nile virus infection Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating West nile virus infection from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

West nile virus infection pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of West nile virus infection pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on West nile virus infection pathophysiology

CDC on West nile virus infection pathophysiology

West nile virus infection pathophysiology in the news

Blogs on West nile virus infection pathophysiology

Directions to Hospitals Treating West nile virus infection

Risk calculators and risk factors for West nile virus infection pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

Overview

The natural reservoir of West Nile virus (WNV) is birds, particularly species with high-level viremia. In contrast, viremia is relatively rare among infected humans, who are considered dead-end hosts of the virus. WNV is transmitted by bites of various species of mosquitoes. Following inoculation, replication of the virus occurs in the Langerhans epidermal dendritic cell. Among immunocompetent hosts, the replication process is immediately followed by activation of the immune system, including complement pathways, and humoral and adaptive immune responses that act simultaneously to clear the infection. On the other hand, immunocompromised patients may suffer CNS dissemination and fatal outcomes due to the failure to activate proper immunological pathways. Finally, the role of genetics in WNV susceptibility is not fully understood; but mice models and a few human experiments have described genetic mutations that may predispose individuals to worse clinical disease of WNV infections.

West Nile virus life cycle

The West Nile virus has an enzootic life cycle, being primarily transmitted between some species of birds and different species of mosquito vectors.[1]

West Nile virus life cycle- Center for Disease Control and Prevention(CDC)[2]

Transmission

Birds are the main reservoir of West Nile virus (WNV). Transmission of the virus is by a mosquito bite of an infected bird with high-level viremia, such as birds of the family Passeriformes.[2] Thus, transmission is frequently denoted as "bird-mosquito-bird" transmission. Other forms of transmission have been speculated, such as direct bird-to-bird transmission, but further validation is still required.[3] Other species may also be infected, such as horses, cats, and dogs. Humans are considered dead-end hosts because the disease rarely progresses to viremia in humans, making transmission of the virus from a human unlikely except in some reported cases of transmission by blood transfusion, breastfeeding, or organ transplantation.[4][5][6]

Mosquitoes responsible for viral transmission belong to different families, varying based on geographical location:[7]

  • Culex pipiens: Northern half and West of USA
  • Culex quinquefasciatus: Southeast and West of USA
  • Culex tarsalis: West of USA

[[

image:WNV Mosquito.png|600px|thumb|center|Approximate geographic distribution of the primary WNV vectors, Cx. pipiens, Cx. quinquefasciatus and Cx. tarsalis- Center for Disease Control and Prevention(CDC)[2]]]

Other transmission routes, not involving vectors, have also been described:[1]

Pathogenesis

Following inoculation, replication of WNV takes place in the Langerhans epidermal dendritic cells, which are antigen-presenting immune cells.[10] These cells then migrate to lymph nodes, resulting in lymph node drainage, followed by viremia and dissemination of the virus into other organs, namely the spleen and the kidneys. Within one week, the virus is successfully cleared from the serum and tissue compartments among immunocompetent individuals. Interferons (IFN) have a crucial role in upregulating genes that carry antiviral functions and in stimulating the maturation of dendritic cells that eventually combine both the innate and the adaptive immune responses.[11] Viral sensors, such as Toll-like receptor 3, help in activation of transcription factors and IFN-stimulated genes.[12][13] Additionally, complement activation through classical, lectin, and alternative pathways offers significant immunity against WNV by opsonization, cytolysis, and chemotaxis. Innate immune cells, such as macrophages, along with humoral, primary, and memory adaptive immune cells are also activated during viral infection; these cells also contribute to the clearance of the virus and the prevention of its dissemination to the CNS.[14]

Mice models have demonstrated that persistent infection, including CNS infiltration, is possible, especially in immunosuppressed states. TNF-alpha has been hypothesized to allow viral migration across the blood-brain barrier (BBB) by promoting the permeability of endothelial cell.[15][16][17] Other reports showed that the virus may cross the BBB either by using the olfactory bulb in a "Trojan horse" mechanism to cross to the CNS, or utilizing passive transport mechanisms, or following a retrograde transport mechanism from peripheral neurons.[18][19][20]

Tropism

WNV may be disseminated to include all organ systems. Animal models demonstrated that WNV infection typically first appears in the lymphatic tissue and the spleen before it migrates to other organs, namely the kidneys, lungs, liver, the cardiovascular system, and the nervous system.[21] In animals, tropism of WNV has been described in the following organs:

  • Eyes
  • Peripheral and central nervous system
  • Heart
  • Blood vessels
  • Spleen and other lymphoid organs
  • Liver
  • Kidneys
  • Lungs
  • GI tract
  • Endocrine system, including gonads
  • Skeletal muscles
  • Skin
  • Bone marrow

Genetics

Genetic factors may be associated with WNV susceptibility. In mice strains, a truncated isoform mutation of the gene encoding OAS1b may lead to susceptibility of infections by WNV and other flaviviruses. Similarly, human subjects with CCR5-Δ32, a mutant allele of the gene encoding chemokine receptor, were more likely to be symptomatic with worse WNV clinical disease. Nonetheless, the true role of genetics in the susceptibility and resistance to WNV is yet to be elucidated.[22][23]

References

  1. ↑ 1.0 1.1 Campbell, Grant L; Marfin, Anthony A; Lanciotti, Robert S; Gubler, Duane J (2002). "West Nile virus". The Lancet Infectious Diseases. 2 (9): 519–529. doi:10.1016/S1473-3099(02)00368-7. ISSN 1473-3099.
  2. ↑ 2.0 2.1 2.2 2.3 "Center for Disease Control and Prevention (CDC)".
  3. ↑ Komar N, Langevin S, Hinten S, Nemeth N, Edwards E, Hettler D; et al. (2003). ; "Experimental infection of North American birds with the New York 1999 strain of West Nile virus" Check |url= value (help). Emerg Infect Dis. 9 (3): 311–22. doi:10.3201/eid0903.020628. PMC 2958552. PMID 12643825.
  4. ↑ Iwamoto M, Jernigan DB, Guasch A, Trepka MJ, Blackmore CG, Hellinger WC; et al. (2003). ; "Transmission of West Nile virus from an organ donor to four transplant recipients" Check |url= value (help). N Engl J Med. 348 (22): 2196–203. doi:10.1056/NEJMoa022987. PMID 12773646.
  5. ↑ Pealer LN, Marfin AA, Petersen LR, Lanciotti RS, Page PL, Stramer SL; et al. (2003). ; "Transmission of West Nile virus through blood transfusion in the United States in 2002" Check |url= value (help). N Engl J Med. 349 (13): 1236–45. doi:10.1056/NEJMoa030969. PMID 14500806.
  6. ↑ Centers for Disease Control and Prevention (CDC) (2002). ; "Possible West Nile virus transmission to an infant through breast-feeding--Michigan, 2002" Check |url= value (help). MMWR Morb Mortal Wkly Rep. 51 (39): 877–8. PMID 12375687.
  7. ↑ Petersen LR, Brault AC, Nasci RS (2013). ; "West Nile virus: review of the literature" Check |url= value (help). JAMA. 310 (3): 308–15. doi:10.1001/jama.2013.8042. PMID 23860989.
  8. ↑ 8.0 8.1 8.2 "Investigations of West Nile Virus Infections in Recipients of Organ Transplantation and Blood Transfusion".
  9. ↑ Iwamoto, Martha; Jernigan, Daniel B.; Guasch, Antonio; Trepka, Mary Jo; Blackmore, Carina G.; Hellinger, Walter C.; Pham, Si M.; Zaki, Sherif; Lanciotti, Robert S.; Lance-Parker, Susan E.; DiazGranados, Carlos A.; Winquist, Andrea G.; Perlino, Carl A.; Wiersma, Steven; Hillyer, Krista L.; Goodman, Jesse L.; Marfin, Anthony A.; Chamberland, Mary E.; Petersen, Lyle R. (2003). "Transmission of West Nile Virus from an Organ Donor to Four Transplant Recipients". New England Journal of Medicine. 348 (22): 2196–2203. doi:10.1056/NEJMoa022987. ISSN 0028-4793.
  10. ↑ Byrne SN, Halliday GM, Johnston LJ, King NJ (2001). ; "Interleukin-1beta but not tumor necrosis factor is involved in West Nile virus-induced Langerhans cell migration from the skin in C57BL/6 mice" Check |url= value (help). J Invest Dermatol. 117 (3): 702–9. doi:10.1046/j.0022-202x.2001.01454.x. PMID 11564180.
  11. ↑ Asselin-Paturel C, Brizard G, Chemin K, Boonstra A, O'Garra A, Vicari A; et al. (2005). "Type I interferon dependence of plasmacytoid dendritic cell activation and migration". J Exp Med. 201 (7): 1157–67. doi:10.1084/jem.20041930. PMC 2213121. PMID 15795237.
  12. ↑ Barton GM, Medzhitov R (2003). "Linking Toll-like receptors to IFN-alpha/beta expression". Nat Immunol. 4 (5): 432–3. doi:10.1038/ni0503-432. PMID 12719735.
  13. ↑ Keller BC, Fredericksen BL, Samuel MA, Mock RE, Mason PW, Diamond MS; et al. (2006). "Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence". J Virol. 80 (19): 9424–34. doi:10.1128/JVI.00768-06. PMC 1617238. PMID 16973548.
  14. ↑ Samuel MA, Diamond MS (2006). "Pathogenesis of West Nile Virus infection: a balance between virulence, innate and adaptive immunity, and viral evasion". J Virol. 80 (19): 9349–60. doi:10.1128/JVI.01122-06. PMC 1617273. PMID 16973541.
  15. ↑ Diamond MS, Sitati EM, Friend LD, Higgs S, Shrestha B, Engle M (2003). ; "A critical role for induced IgM in the protection against West Nile virus infection" Check |url= value (help). J Exp Med. 198 (12): 1853–62. doi:10.1084/jem.20031223. PMC 2194144. PMID 14662909.
  16. ↑ Samuel MA, Diamond MS (2005). ; "Alpha/beta interferon protects against lethal West Nile virus infection by restricting cellular tropism and enhancing neuronal survival" Check |url= value (help). J Virol. 79 (21): 13350–61. doi:10.1128/JVI.79.21.13350-13361.2005. PMC 1262587. PMID 16227257.
  17. ↑ Wang T, Town T, Alexopoulou L, Anderson JF, Fikrig E, Flavell RA (2004). ; "Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis" Check |url= value (help). Nat Med. 10 (12): 1366–73. doi:10.1038/nm1140. PMID 15558055.
  18. ↑ Kramer-Hämmerle S, Rothenaigner I, Wolff H, Bell JE, Brack-Werner R (2005). ; "Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus" Check |url= value (help). Virus Res. 111 (2): 194–213. doi:10.1016/j.virusres.2005.04.009. PMID 15885841.
  19. ↑ Monath TP, Cropp CB, Harrison AK (1983). ; "Mode of entry of a neurotropic arbovirus into the central nervous system. Reinvestigation of an old controversy" Check |url= value (help). Lab Invest. 48 (4): 399–410. PMID 6300550.
  20. ↑ Garcia-Tapia D, Loiacono CM, Kleiboeker SB (2006). ; "Replication of West Nile virus in equine peripheral blood mononuclear cells" Check |url= value (help). Vet Immunol Immunopathol. 110 (3–4): 229–44. doi:10.1016/j.vetimm.2005.10.003. PMID 16310859.
  21. ↑ Gamino V, Höfle U (2013). "Pathology and tissue tropism of natural West Nile virus infection in birds: a review". Vet Res. 44: 39. doi:10.1186/1297-9716-44-39. PMC 3686667. PMID 23731695.
  22. ↑ Glass WG, McDermott DH, Lim JK, Lekhong S, Yu SF, Frank WA; et al. (2006). ; "CCR5 deficiency increases risk of symptomatic West Nile virus infection" Check |url= value (help). J Exp Med. 203 (1): 35–40. doi:10.1084/jem.20051970. PMC 2118086. PMID 16418398.
  23. ↑ Yakub I, Lillibridge KM, Moran A, Gonzalez OY, Belmont J, Gibbs RA; et al. (2005). ; "Single nucleotide polymorphisms in genes for 2'-5'-oligoadenylate synthetase and RNase L inpatients hospitalized with West Nile virus infection" Check |url= value (help). J Infect Dis. 192 (10): 1741–8. doi:10.1086/497340. PMID 16235172.


Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=West_nile_virus_infection_pathophysiology&oldid=1360663"