Persistent Infection with West Nile Virus

Abstract & Commentary

By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.

Synopsis: West Nile Virus (WNV) RNA was demonstrated by reverse transcriptase PCR (RT-PCR) in the urine of five of 25 convalescent patients 1.6-6.7 years following infection. Sequence analysis showed > 99% homology to the WNV NY99 strain.

Source: Murray K, et al. Persistent infection with West Nile virus years after initial infection. J Infect Dis. 2010; 201:2-4.

A longitudinal study of hospitalized WNV patients in Houston was initiated in 2002. A total of 112 patients remain in the cohort. Patients are assessed clinically, and blood is drawn every six months. At one year post-infection, approximately 60% of patients remain symptomatic. Chronic symptoms appear to be associated with persistence of anti-WNV IgM antibody, elevated plasma levels of interferon gamma-inducing protein (possibly indicating persistent infection), and evidence of suppression of type 2 T-helper pathway (possibly indicating immunosilencing as a mechanism facilitating viral persistence).

Fresh urine was collected from 25 patients between 573 and 2,452 days after onset of acute infection. First round RT-PCR, followed by nested PCR, was performed on these samples. Five samples yielded amplicons, of which four were able to be sequenced. Sequence analysis of these four amplicons revealed > 99% sequence homology to the WNV NY99 strain. Four of the five PCR-positive patients reported chronic symptoms; all were elderly men who had initially presented with encephalitis.

Commentary

West Nile virus, an epizootic flavivirus, first appeared in the United States in 1999 and, over the next few years, made its way across the entire continent, initially infecting birds (the natural reservoir for this virus) and, transmitted by a mosquito vector, quickly infected humans. The spectrum of clinical illness ranges from minimally symptomatic infection, to West Nile fever, to encephalitis. Particularly in elderly adults, the encephalitis was often associated with flaccid paralysis, a high mortality rate, and a high frequency of neurologic sequelae and nonspecific symptoms in survivors. A hamster model of WNV infection demonstrated persistent viral replication in the kidneys of experimentally infected animals. This study suggests that similar ongoing WNV replication occurs in at least some more severely affected humans. Interestingly, in the larger cohort, five patients developed chronic renal failure and died during the follow-up period, raising the possibility that WNV may be nephropathic in some patients.

This finding of ongoing WNV viral replication in humans (if confirmed by other investigators) has significant implications for public health, since this suggests that humans (as well as birds) could be an important reservoir for transmission to mosquitoes. It also suggests that humans (rather than mosquitoes hitch-hiking in aircraft) may have been the route by which WNV first arrived in North America in 1999.