Scrapie in mice. Agent-strain differences in the distribution and intensity of grey matter vacuolation.

C57BL/6J mice infected intravenously with the Sarafend strain of West Nile virus (WNV) develop a characteristic central nervous system (CNS) disease, including an acute inflammatory reaction. Dose response studies indicate two distinct kinetics of mortality. At high doses of infection (10(8) PFU), direct infection of the brain occurred within 24 h, resulting in 100% mortality with a 6-day mean survival time (MST), and there was minimal destruction of neural tissue. A low dose (10(3) PFU) of infection resulted in 27% mortality (MST, 11 days), and virus could be detected in the CNS 7 days postinfection (p.i.). Virus was present in the hypogastric lymph nodes and spleens at days 4 to 7 p.i. Histology of the brains revealed neuronal degeneration and inflammation within leptomeninges and brain parenchyma. Inflammatory cell infiltration was detectable in brains from day 4 p.i. onward in the high-dose group and from day 7 p.i. in the low-dose group, with the severity of infiltration increasing over time. The cellular infiltrates in brain consisted predominantly of CD8(+), but not CD4(+), T cells. CD8(+) T cells in the brain and the spleen expressed the activation markers CD69 early and expressed CD25 at later time points. CD8(+) T-cell-deficient mice infected with 10(3) PFU of WNV showed increased mortalities but prolonged MST and early infection of the CNS compared to wild-type mice. Using high doses of virus in CD8-deficient mice leads to increased survival. These results provide evidence that CD8(+) T cells are involved in both recovery and immunopathology in WNV infection.

CD8+ T Cells Mediate Recovery and Immunopathology in West Nile Virus Encephalitis

The flavivirus E glycoprotein, the primary antigen that induces protective immunity, is essential for membrane fusion and mediates binding to cellular receptors. Human flavivirus infections stimulate virus species-specific as well as flavivirus cross-reactive immune responses. Flavivirus cross-reactive antibodies in human sera create a serious problem for serodiagnosis, especially for secondary flavivirus infections, due to the difficulty of differentiating primary from secondary cross-reactive serum antibodies. The presence of subneutralizing levels of flavivirus cross-reactive serum antibodies may result in a dramatic increase in the severity of secondary flavivirus infections via antibody-dependent enhancement. An understanding of flavivirus E-glycoprotein cross-reactive epitopes is therefore critical for improving public health responses to these serious diseases. We identified six E-glycoprotein residues that are incorporated into three distinct flavivirus cross-reactive epitopes. Two of these epitopes which are recognized by distinct monoclonal antibodies contain overlapping continuous residues located within the highly conserved fusion peptide. The third epitope consists of discontinuous residues that are structurally related to the strictly conserved tryptophan at dengue virus serotype 2 E-glycoprotein position 231.

https://jvi.asm.org/content/jvi/78/24/13975.full.pdf

Localization and Characterization of Flavivirus Envelope Glycoprotein Cross-Reactive Epitopes

WNV continues to spread throughout the Western Hemisphere as virus activity in insects and animals has been reported in the United States, Canada, Mexico, and the Caribbean islands West Nile virus (WNV) infects the central nervous system and causes severe disease primarily in humans who are immunocompromised or elderly In this review, we discuss the mechanisms by which the immune system limits dissemination of WNV infection Recent experimental studies in animals suggest important roles for both the innate and the adaptive immune responses in controlling WNV infection Interferons, antibody, complement components and CD8+ T cells coordinate protection against severe infection and disease These findings are analyzed in the context of recent approaches to vaccine development and immunotherapy against WNV

Innate and adaptive immune responses determine protection against disseminated infection by West Nile encephalitis virus.

Crow deaths were observed after West Nile virus (WNV) was introduced into North America, and this phenomenon has subsequently been used to monitor the spread of the virus. To investigate potential differences in the crow virulence of different WNV strains, American Crows were inoculated with Old World strains of WNV from Kenya and Australia (Kunjin) and a North American (NY99) WNV genotype. Infection of crows with NY99 genotype resulted in high serum viremia levels and death; the Kenyan and Kunjin genotypes elicited low viremia levels and minimal deaths but resulted in the generation of neutralizing antibodies capable of providing 100% protection from infection with the NY99 strain. These results suggest that genetic alterations in NY99 WNV are responsible for the crow-virulent phenotype and that increased replication of this strain in crows could spread WNV in North America.

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Differential virulence of West Nile strains for American crows.

Protection against west nile virus induced by a previous injection with dengue virus

Histological studies of the monkey neurovirulence of group b arboviruses i. a semiquantitative grading scale

In the assessment of neuropathological changes in primates occurring after inoculation of neurovirulent viruses into the central nervous system, it would clearly be valuable to know which areas are consistently affected by these viruses. 72 rhesus monkeys were inoculated intracerebrally with 1 of 5 group B arboviruses (Japanese encephalitis, Langat, West Nile, yellow fever, dengue 4) or with poliovirus 3 or control Other CABI sites 

Histological studies of the monkey neurovirulence of group B arboviruses. II. Selection of indicator centers.

The protection afforded by similar concentrations of different dengue virus serotypes against a subsequent challenge of West Nile virus was studied in hamsters. The New Guinea C strain of dengue 2 virus gave the best protection. It was found that the anamnestic neutralizing antibody response induced by the challenge West Nile virus against West Nile virus in hamsters, previously immunized with dengue 2 virus, might play a major role in the cross-protection observed in this system.

/pdf/the-mechanism-of-cross-protection-afforded-by-dengue-virus-41hnm6jncm.pdf

Inderjit S. Thind

Papers

Protection against west nile virus induced by a previous injection with dengue virus

Histological studies of the monkey neurovirulence of group b arboviruses i. a semiquantitative grading scale

Histological studies of the monkey neurovirulence of group B arboviruses. II. Selection of indicator centers.

The mechanism of cross-protection afforded by dengue virus against West Nile virus in hamsters.

A chick embryo attenuated strain (TP21 E5) of Langat virus. I. Virulence of the virus for mice and monkeys.