Immunological Cross-Reactivity to Dengue Virus among Persons with Neuroinvasive West Nile Virus Infection

Antibody dependent enhancement has been well described between Zika and dengue viruses, but is poorly characterized between West Nile and dengue viruses. We demonstrate that neuroinvasive West Nile virus infection leads to the development of non-neutralizing, cross-reactive IgG antibodies to dengue and Zika viruses capable of causing antibody dependent enhancement in vitro of dengue virus and leads to the formation of flavivirus cross-reactive memory B cells in some patients.

Global Seroprevalence of West Nile Virus in Horses of Morocco

West Nile Fever (WNF) is a viral emerging mosquito-borne disease causing mortality and morbidity with varying severity (from mild fever to severe neuroinvasive disease) among human and animal populations in many parts of the world. The current study aimed to confirm the virus circulation and assess the disease seroprevalence in horses of Morocco. A sample of 1171 healthy non-vaccinated (against-WNF) horses, taken from 11 (out of 12) regions of the country during July-December 2016, was primarily tested using competitive ELISA assay (cELISA). All cELISA-reactive positive and doubtful sera (n= 269) were further tested by virus neutralization test (VNT). The results of cELISA test revealed an overall WNF seroprevalence in 21.8% (255/1171) of sampled horses. This rate decreased to 18.8% (220/1171) after the confirmation of VNT. The WNF seroprevalence in the current study varied significantly by age, gender, and breed of the tested horses. Indeed, the higher seropositivity rates were found in the oldest (27.7%), female (22.0%), and saddle (32.1%) horses. However, the origin of animals did not show any significant effect on the West Nile virus infection. The obtained results of the present study, therefore, provided serological and epidemiological evidence of the endemicity of the WNV in horse populations of Morocco.

The seroepidemiology and risk factors of West Nile virus infection in blood donors of Fars province, southwest of Iran

Aim: To evaluate the frequency of West Nile virus (WNV) in blood donors of the blood transfusion center of Fars province, Iran. Materials & methods: A total of 337 participants referred for blood donation to Fars blood centers were included. The presence of anti-WNV antibodies was analyzed using the WNV IgG ELISA kit. Results: Out of all participants, 76 (22.6%) were positive for anti-WNV IgG antibodies. Our results also showed that the frequency of WNV was associated with the age, educational level, job and city of residency of participants (p < 0.05). Conclusion: The results indicated the high frequency of WNV seropositivity among blood donors in southwest Iran. Accordingly, there is an urgent need to establish an integrated surveillance system for monitoring WNV infection in Iran.

Case Report: Neurologic Presentation of West Nile Virus: Difficult Diagnosis

West Nile virus infections have surged across the globe. South Texas, located on the path of bird migration, with Culex quinquefasciatus and other Culex species, and biotic primers that predispose the area to epidemics (floods, amplifying hosts, and lack of mosquito control and prevention) remains a highly endemic area for arbovirus spread. West Nile virus infection ranges from mild febrile illness to severe central nervous system involvement. The purpose of this report is to highlight complex presentations of WNV and how confounding presenting symptoms delay diagnosis. The secondary goal is to describe how pandemics, such as SARS-CoV-2, can overwhelm the system and result in medical decision bias errors.

Human Monoclonal Antibodies against NS1 Protein Protect against Lethal West Nile Virus Infection

Therapeutic antibodies against flaviviruses often promote neutralization by targeting the envelope protein of the virion. However, this approach is hindered by a possible concern for antibody-dependent enhancement of infection and paradoxical worsening of disease.

Development of peptides targeting receptor binding site of the envelope glycoprotein to contain the West Nile virus infection

West Nile virus (WNV), re-emerging neurotropic flavivirus, can cross the blood–brain barrier (BBB) and cause fatal encephalitis and meningitis. Infection of the human brain microvascular endothelial cells (hBMECs), building blocks of the BBB, represents the pivotal step in neuroinvasion. Domain III (DIII) of the envelope (E) glycoprotein is a key receptor-binding domain, thus, it is an attractive target for anti-flavivirus strategies. Here, two combinatorial phage display peptide libraries, Ph.D.-C7C and Ph.D.-12, were panned against receptor-binding site (RBS) on DIII to isolate peptides that could block DIII. From series of pannings, nine peptides (seven 7-mer cyclic and two 12-mer linear) were selected and overexpressed in E. coli SHuffle T5. Presence of disulfide bond in 7-mer peptides was confirmed with thiol-reactive maleimide labeling. Except for linear peptide 19 (HYSWSWIAYSPG), all peptides proved to be DIII binders. Among all peptides, 4 cyclic peptides (CTKTDVHFC, CIHSSTRAC, CTYENHRTC, and CLAQSHPLC) showed significant blocking of the interaction between DIII and hBMECs, and ability to neutralize infection in cultured cells. None of these peptides showed toxic or hemolytic activity. Peptides identified in this study may serve as potential candidates for the development of novel antiviral therapeutics against WNV.

The Effect of Fluctuating Incubation Temperatures on West Nile Virus Infection in Culex Mosquitoes

Temperature plays a significant role in the vector competence, extrinsic incubation period, and intensity of infection of arboviruses within mosquito vectors. Most laboratory infection studies use static incubation temperatures that may not accurately reflect daily temperature ranges (DTR) to which mosquitoes are exposed. This could potentially compromise the application of results to real world scenarios. We evaluated the effect of fluctuating DTR versus static temperature treatments on the infection, dissemination, and transmission rates and viral titers of Culex tarsalis and Culex quinquefasciatus mosquitoes for West Nile virus. Two DTR regimens were tested including an 11 and 15 °C range, both fluctuating around an average temperature of 28 °C. Overall, no significant differences were found between DTR and static treatments for infection, dissemination, or transmission rates for either species. However, significant treatment differences were identified for both Cx. tarsalis and Cx. quinquefasciatus viral titers. These effects were species-specific and most prominent later in the infection. These results indicate that future studies on WNV infections in Culex mosquitoes should consider employing realistic DTRs to reflect interactions most accurately between the virus, vector, and environment.