Neurological Implications of Zika Virus Infection in Adults

Abstract

The 2015-2016 epidemic of Zika virus (ZIKV) in the Americas and the Caribbean was associated with an unprecedented burden of neurological disease among adults. Clinically, Guillain-Barre syndrome (GBS) predominated among regions affected by the ZIKV epidemic, but the spectrum of neurological disease in the adults appears broader as cases of encephalopathy, encephalitis, meningitis, myelitis, and seizures have also been reported. A para-infectious temporal profile of ZIKV-associated GBS (ZIKV-GBS) has been described in clinical studies, which may suggest a direct viral neuropathic effect. However, ZIKV neuropathogenesis has not yet been fully understood. Mechanisms for ZIKV-GBS and other neurological syndromes have been hypothesized, such as adaptive viral genetic changes, immunological interactions with other circulating flaviviruses, and host and factors. This review summarizes the current evidence on ZIKV-associated neurological complications in the adults.

Keywords: Guillain-Barre syndrome; Zika virus; adult population; neurological disease.

Figure 1.

Cases of Zika virus (ZIKV) disease, ZIKV-associated Guillain-Barre syndrome (GBS), and ZIKV-associated neurological disease in Colombia, by epidemiological week. The cumulative incidence of GBS from October 2015 to epidemiological week 9 of 2016 was 220 cases (red asterisk). Data are based on findings reported elsewhere [17].

Figure 2.

Speculated mechanisms for Zika virus (ZIKV)–associated neurological disease. A, Antibody-dependent enhancement (ADE) of infection. Anti-envelope (E) or anti-premembrane (prM) immunoglobulin G (IgG) antibodies elicited by previous flavivirus infection fail to neutralize ZIKV but instead enhance the capture of these complexes by cells expressing FcγR (eg, macrophages), which ultimately increases the ZIKV load, promoting disease. B, Anti-ZIKV IgG antibodies attach to antigens in the peripheral nerves (ie, cross-reactivity), which activates the complement system and triggers local inflammation driven by macrophages. C, Antigen-presenting cells (APCs) present ZIKV-derived peptides on class II major histocompatibility complex (MHC) molecules to naive CD4⁺ T lymphocytes, driving activation of these cells and inflammation. Cytokines and inflammatory cells are attracted to the peripheral nervous system, mediating peripheral nerve injury. D, ZIKV infects Schwann cells/neurons and causes cytopathic effects; viral infection activates CD8⁺ T lymphocytes, causing cytotoxicity and peripheral nerve injury.