Is the ZIKV Congenital Syndrome and Microcephaly Due to Syndemism with Latent Virus Coinfection?

Abstract

The emergence of the Zika virus (ZIKV) mirrors its evolutionary nature and, thus, its ability to grow in diversity or complexity (i.e., related to genome, host response, environment changes, tropism, and pathogenicity), leading to it recently joining the circle of closed congenital pathogens. The causal relation of ZIKV to microcephaly is still a much-debated issue. The identification of outbreak foci being in certain endemic urban areas characterized by a high-density population emphasizes that mixed infections might spearhead the recent appearance of a wide range of diseases that were initially attributed to ZIKV. Globally, such coinfections may have both positive and negative effects on viral replication, tropism, host response, and the viral genome. In other words, the possibility of coinfection may necessitate revisiting what is considered to be known regarding the pathogenesis and epidemiology of ZIKV diseases. ZIKV viral coinfections are already being reported with other arboviruses (e.g., chikungunya virus (CHIKV) and dengue virus (DENV)) as well as congenital pathogens (e.g., human immunodeficiency virus (HIV) and cytomegalovirus (HCMV)). However, descriptions of human latent viruses and their impacts on ZIKV disease outcomes in hosts are currently lacking. This review proposes to select some interesting human latent viruses (i.e., herpes simplex virus 2 (HSV-2), Epstein–Barr virus (EBV), human herpesvirus 6 (HHV-6), human parvovirus B19 (B19V), and human papillomavirus (HPV)), whose virological features and co-exposition with ZIKV may provide evidence of the syndemism process, shedding some light on the emergence of the ZIKV-induced global congenital syndrome in South America.

Microcephaly and Associated Risk Factors in Newborns: A Systematic Review and Meta-Analysis Study

“…It has long been hypothesized that congenital infections beyond TORCH can also contribute to microcephaly [ 38 , 39 ]. Abnormal placental morphologic changes (higher area, perimeter, sprouts, and inflammatory responses) can occur in pregnant women positive for human immunodeficiency virus (HIV) [ 40 ].…”

HSV-2 Infection Enhances Zika Virus Infection of Primary Genital Epithelial Cells Independently of the Known Zika Virus Receptor AXL

“…Clinical reports indicate the coinfections of ZIKV and other pathogens are possible ( Grayo, 2021 ). There is scarce data explaining the mechanisms underlying viral synergism; to the best of our knowledge, only one study explored HSV-ZIKV coinfection and the cellular model was first-trimester trophoblastic cells ( Aldo et al, 2016 ), which are not typical host cells for HSV.…”

Big Data to Knowledge Analytics Reveals the Zika Virus Epidemic as Only One of Multiple Factors Contributing to a Year-Over-Year 28-Fold Increase in Microcephaly Incidence

“…Inside the country, the burden of Zika-related microcephaly disproportionately affected the northeast states of Pernambuco and Bahia [ 9 , 10 ]. Therefore, some public health actions, including the use of larvicides [ 11 , 12 , 13 , 14 ] and vaccinations [ 15 ], as well as possible environmental, socioeconomic, or biological factors [ 16 , 17 , 18 ], emerged as likely alternative explanations for the uneven microcephaly distributions. By technical assessments, the WHO began to dispel some of these associations [ 19 ].…”