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Review
. 2023 Nov 24:13:1284651.
doi: 10.3389/fcimb.2023.1284651. eCollection 2023.

Flying under the radar - impact and factors influencing asymptomatic DENV infections

Affiliations
Review

Flying under the radar - impact and factors influencing asymptomatic DENV infections

Paulo Henriques et al. Front Cell Infect Microbiol. .

Abstract

The clinical outcome of DENV and other Flaviviruses infections represents a spectrum of severity that ranges from mild manifestations to severe disease, which can ultimately lead to death. Nonetheless, most of these infections result in an asymptomatic outcome that may play an important role in the persistent circulation of these viruses. Also, although little is known about the mechanisms that lead to these asymptomatic infections, they are likely the result of a complex interplay between viral and host factors. Specific characteristics of the infecting viral strain, such as its replicating efficiency, coupled with host factors, like gene expression of key molecules involved in the immune response or in the protection against disease, are among crucial factors to study. This review revisits recent data on factors that may contribute to the asymptomatic outcome of the world's widespread DENV, highlighting the importance of silent infections in the transmission of this pathogen and the immune status of the host.

Keywords: DENV infection; asymptomatic infections; dengue; flavivirus infections; host factors.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of DENV transmission. DENV infection in humans is initiated after the virus is delivered into the host’s skin, during a blood meal of an infected female Aedes sp. mosquito. One mosquito can infect several humans, as it can bite several times before completing oogenesis. Some of the infected humans will develop dengue symptoms after 4-10 days of virus incubation, while others will remain asymptomatic or have an inapparent infection (World Health Organization, 2009). Both symptomatic and asymptomatic humans may have sufficiently high viremia to infect mosquitoes during their feeding. After a period of 8-12 days, mosquitoes are able to infect humans (World Health Organization, 2009). Diagram was made using BioRender.com.
Figure 2
Figure 2
Factors likely influencing the clinical protection in individuals experiencing a DENV primary infection. Different viral serotypes/genotypes may have distinct abilities to infect human cells and/or replicate, thus influencing the viral load and the course of infection. DENV4 is more commonly referred to as causing a higher proportion of asymptomatic infections and is also associated with a lower replication efficiency. In the same line, the size of the viral inoculum introduced during the mosquito blood feeding may locally trigger different immune responses and/or lead to different viremias. Additionally, the metabolic status of the host, and in particular his nutritional status and lipid profile may contribute to the asymptomatic outcome in a primary DENV infection, either by regulating viremia or modulating the host’s immune response and/or epigenetic patterns. Host genetic variants and differential expression levels (likely mediated by epigenetic patterns) have also been associated with protection against clinical dengue. This is the case of genes coding for receptors used by DENV to infect human cells and mediators of the immune response or disease tolerance. In turn, age influences the host’s metabolic status, epigenetic patterns, and immune response, being commonly found in the literature that asymptomatic DENV infections are more frequent in children up to middle childhood, when compared to upper childhood and adulthood. The host’s immune response, including mechanisms of disease tolerance and trained immunity, as an epigenetic reprogramming of innate immune cells induced by previous exposition to unrelated pathogens, can also influence the outcome of DENV infection. Also, the protective immune mechanisms primed by the pre-exposition of the host to proteins of the mosquito saliva should be here considered. Note that the host’s metabolic status, genetics, epigenetics, and age are not independent factors and, together with viral factors, can as well influence the immune status of the host. Diagram was made using BioRender.com.

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