Emerging Infections of CNS: Avian Influenza A Virus, Rift Valley Fever Virus and Human Parechovirus

Abstract

History is replete with emergent pandemic infections that have decimated the human population. Given the shear mass of humans that now crowd the earth, there is every reason to suspect history will repeat itself. We describe three RNA viruses that have recently emerged in the human population to mediate severe neurological disease. These new diseases are results of new mutations in the infectious agents or new exposure pathways to the agents or both. To appreciate their pathogenesis, we summarize the essential virology and immune response to each agent. Infection is described in the context of known host defenses. Once the viruses evade immune defenses and enter CNS cells, they rapidly co-opt host RNA processing to a cataclysmic extent. It is not clear why the brain is particularly susceptible to RNA viruses; but perhaps because of its tremendous dependence on RNA processing for physiological functioning, classical mechanisms of host defense (e.g. interferon disruption of viral replication) are diminished or not available. Effectiveness of immunity, immunization and pharmacological therapies is reviewed to contextualize the scope of the public health challenge. Unfortunately, vaccines that confer protection from systemic disease do not necessarily confer protection for the brain after exposure through unconventional routes.

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

“…While the overall mortality rate for severe RFVF infections is < 1 %, it may approach 50 % in hemorrhagic cases. Neuropathologic findings include diffuse perivascular infiltrates of lymphocytes and macrophages, multifocal meningitis, and focal areas of neuronal necrosis and aggregates of macrophages, lymphocytes, and neutrophils throughout all regions of the brain [79].…”

Global research trends of World Health Organization’s top eight emerging pathogens

“…Nipah virus, identified in 1998, is emerging zoonosis that affects both animals and humans [13,[21][22][23][24]. Rift Valley fever is a viral zoonosis that was first identified among sheep on a farm in the Rift Valley of Kenya [25][26][27][28][29]. The WHO committee listed another three pathogens/infectious diseases and considered them as serious and require an action as soon as possible.…”

“…Literature review using Pubmed, Google Scholar and Scopus showed that bibliometric studies on SARS or Ebola or Nipah virus have been carried out, but as a single disease and not as a group of diseases with potential future severe epidemics [25][26][27][28][29]. The collective analysis of literature on top eight pathogens will give a more comprehensive view on these infectious diseases and will help identify which one needs to be given top priority for funding and research.…”

Keeping it in check: chronic viral infection and antiviral immunity in the brain

“…Limits of detection, reproducibility, consistency in the brain regions that are analysed and patient-to-patient variability all contribute to the challenges and dangers of ascribing neurotropic infections to be the aetiologic causes of poorly understood CNS diseases. Moreover, the association of 'new' viruses with CNS disease (including Zika virus, which is linked to microcephaly 108,109 ) or the emergence of more neurovirulent influenza strains 110 are reminders that our understanding of the pathogenic consequences of CNS infections remain quite primitive. Translational studies have provided insights into the links between infections and disease but are not without controversy.…”