Scientific journal
European Journal of Natural History
ISSN 2073-4972

MORPHOLOGICAL ALTERATIONS IN THE LUNGS DURING WEST NILE VIRUS INFECTION

Smirnov A.V., Pisarev V.B., Bikchalov L.S.
West Nile virus (WNV) is an enveloped, neurotropic, single stranded (+) sense RNA flavivirus, first isolated from a woman in Uganda in 1937 (Smithburn K.C. et al., 1940). Since then it has reemerged multiple times: first in Europe, Asia and most recently during the 1999 in the Volgograd Region of Russia and in the United States (Hubalek Z., Halouzka J., 1999; Lanciotti R.S. et al., 1999; Pisarev V.B. et al., 2000). The virus, which has spread rapidly throughout Volgograd Region, may cause severe illness especially in the elderly (manifested by meningitis and encephalitis) that may lead to paralysis, coma, and death. During the 1999-2002 outbreaks of WNV in the Volgograd Region, more 1,000 cases were reported, including 18 deaths ( 1.8%) (Lvov D.K. et al., 2004). Central nervous system (CNS) expression of the chemokine receptor CCR5 and its ligand CCL5 was prominently up-regulated by WNV, and this was associated with CNS infiltration of CD4+ and CD8+ T cells, NK1.1+ cells and macrophages expressing the receptor. It is considered CCR5 is a critical antiviral and survival determinant in WNV infection of mice that acts by regulating trafficking of leukocytes to the infected brain (Glass W.G. et al., 2005).

In the Volgograd Region 23.6% cases of West Nile fever during the 1999-2002 without meningitis and encephalitis were reported (Petrov V.A., 2004). WNV infection leads to morphological alterations in different organs. Postmortal  examination has found  mononuclear aggregations in bronchial walls, perivascular mononuclear infiltration, pulmonary edema and focal hemorrhages, but clinical alterations of respiratory functions were not detected (Grigoryeva N.V., 2005). The morphological pathogenesis of pulmonary WNV infection is poorly understood.

Here, we characterize a mouse model for WNV infection using a intraperitoneal route of infection. White mice were infected i.p. with 103 focus-forming units (ffu) of strain WNV Astr 986, identical to WNV-NY99, which imitates the natural route of WNV infection in man. Mortality was 20% at that dose. The grope of surviving mice constitutes 8 animals. Lungs obtained from mice at day 9 after induction of WNV infection were fixed in 10% (weight/volume) neutral buffered formalin, were embedded in paraffin and were cut into sections 5 µm in thickness. Sections were stained with hematoxylin and eosin for routine histological analysis.

In pulmonary bronchi mononuclear aggregations in bronchial walls were found. They occupied all layers, but the most prominent density of small lymphocytes was in the adventitia. Lymphoid infiltration spreads on the surrounding tissues and was more prominent around small blood vessels. Hemodynamic changes were also found: hyperemia, stasis in capillaries, perivascular hemorrhages. Interalveolar septa were edematous, infiltrated by small lymphocytes and macrophages. Alveolocytes were edematous, some of them desquamated. Inside alveoli serous liquid was found, but in some cases hemorrhagic infarctions were detected.

Intrapulmonary autonomic ganglia contained polygonal neurons with vacuolated cytoplasm of perikarya. They nuclei were rounded vesicular with one or two ectopic nucleoli. Part of neurons had hyperchromic cytoplasm of perikarya. Satellite neuroglial cells were with minimal dystrophic alterations. Lymphoid infiltration and interstitial edema of ganglionar capsule and stroma were found.

Our findings suggest that endothelial cells in the lungs of WNV infected  mice regulate migration of leukocytes to the infected lung. The damage of peripheral nervous system participates in pathogenesis WNV infection. The data also raise important new questions about the potential roles of regulatory systems that are induced by WNV in this model and in man.

The article is admitted to the International Scientific Conference "Homeostasis and Endoecology", Egypt, Hurgada, February, 21-28, 2007; came to the editorial office on 17.01.07