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.

West Nile Virus Capsid Degradation of Claudin Proteins Disrupts Epithelial Barrier Function

“…At that time, animals show a fairly widespread infection, including infection of most neurons except for cerebellar granular neurons (data not shown). There is a broad distribution of other infected organs, similar to that reported in autopsies of infected immunosuppressed humans (4). Immunofluorescent staining of kidney sections using antibodies to WNV demonstrate occasional infected renal tubules (Fig.…”

“…Analyses of tissues obtained from WNV-infected humans, hamsters, or mice have revealed that epithelial cells are important targets of viral infection (4,20,51) in such organs as the kidney, intestine, testes, and bile duct. In these tissues, epithelial cells form TJ, resulting in barrier formation.…”

“…Infection of kidney epithelium has also been found in WNVinfected mice (20) and dogs (12). In WNV-infected humans, epithelial cell infection has also been demonstrated in several organs, including the kidney, lung, pancreas, thyroid, intestine, and testes (4). These studies suggest that the epithelial cells may play an important role in WNV pathogenesis.…”

“…At 10 to 16 days p.i., when mice appeared moribund, they were sacrificed and individual organs harvested and fixed in Streck tissue fixative (Streck Laboratories). WNV-infected cells were detected by immunofluorescent staining with rabbit anti-WNV antiserum and claudin-2 and occludin antibodies as described previously (4).…”

The contribution of rodent models to the pathological assessment of flaviviral infections of the central nervous system

“…In many cases, religious and cultural concerns have greatly restricted access to tissue samples from cadavers. Moreover, the distribution of virus and histopathological changes in the brain vary markedly depending on the time taken for different individuals to succumb to infection [104] and their immune status [6]. Additionally, post-mortem human specimens only provide a snapshot of pathological markers and virus distribution in the terminal phase of disease.…”