Systemic distribution of West Nile virus infection: postmortem immunohistochemical study of six cases

Abstract

Rare cases of West Nile virus (WNV)-associated inflammation outside the central nervous system (CNS) have been reported. We evaluated the systemic distribution of WNV in postmortem tissues during encephalitis in six patients using immunohistochemistry. WNV antigens were detected in neurons of CNS (all 6 cases), kidney (4 cases), lungs (2 cases), pancreas (2 cases), thyroid (2 cases), intestine (2 cases), stomach (1 case), esophagus (1 case), bile duct (1 case), skin (1 case), prostate (1 case) and testis (1 case). In systemic organs epithelial cells were infected. In none of the six cases were viral antigens identified in hepatocytes, heart, adrenal gland, nerves, skeletal muscles, bone, vessels and fat. All cases in which viral antigens were identified in systemic organs in addition to CNS were severely immunocompromised transplant recipients. With the exception of testis and brain, most foci of infection were not associated with inflammation. While the absence of inflammation may in part be due to patient immunosuppression or to possible transient nature of any host response, compartmentalization of viral antigen to the luminal region of epithelial cells may sequester WNV from immune recognition. Comparison of our findings with previous reports suggests that patients with WNV encephalitis can have widespread systemic infection.

Figure 1

Examples of H&E (A,C,E,G,I,K) and immunofluorescent distribution of WNV antigen (Green; B,D,F,H,J,L) are demonstrated from Case 2. Kidney (Figure 1A,B) shows abundant viral antigen in select distal renal tubules. WNV antigen is particularly focused on the epithelial surface independent of the minimal inflammatory response present. Lung tissue (C,D) shows moderate autolysis and minimal inflammation despite abundant WNV antigen on apical surface of bronchial epithelium. Exocrine pancreas (E,F) showed no inflammation despite abundant regions of epithelial WNV infection. In the liver (G,H) viral antigen was limited to select regions of the bile duct epithelium. For the most part the skin (I,J) showed no inflammation despite abundant WNV antigen within eccrine glands. The testes (K,L) were severely inflamed and showed abundant WNV antigen within portions of the seminiferous tubules. H&E = hematoxylin and eosin; WNV = West Nile virus.

Figure 2

Top images: Paraffin section of human brain with WNV encephalitis immunostained for macrophages (CD68‐Red) and WNV (Green), show infected neurons in region of macrophage infiltration. Occasional neurons appear to be engulfed by ameboid macrophages. Bottom images: Paraffin section of human brain with WNV encephalitis immunostained for T‐cells (CD3‐Red) and WNV (Green), show infected neurons with infiltrating CD3 T‐cells. Occasional T‐cell nodules surround fragmented neurons. WNV = West Nile virus.

Figure 3

Paraffin section of intestine immunostained for epithelial cells (Pancytokeratin‐Red) and WNV (Green) shows infected epithelial cells containing viral antigen predominantly in cytoplasm on the apical side of the nuclei. WNV = West Nile virus.