An update on the aspects of Zika virus infection on male reproductive system

Abstract

Zika virus (ZIKV) is mainly transmitted through Aedes mosquito bites, but sexual and post-transfusion transmissions have been reported. During acute infection, ZIKV is detectable in most organs and body fluids including human semen. Although it is not currently epidemic, there is a concern that the virus can still reemerge since the male genital tract might harbor persistent reservoirs that could facilitate viral transmission over extended periods, raising concerns among public health and assisted reproductive technologies (ART) experts and professionals. So far, the consensus is that ZIKV infection in the testes or epididymis might affect sperm development and, consequently, male fertility. Still, diagnostic tests have not yet been adapted to resource-restricted countries. This manuscript provides an updated overview of the cellular and molecular mechanisms of ZIKV infection and reviews data on ZIKV persistence in semen and associated risks to the male reproductive system described in human and animal models studies. We provide an updated summary of the impact of the recent ZIKVoutbreak on human-ART, weighing on current recommendations and diagnostic approaches, both available and prospective, with special emphasis on mass spectrometry-based biomarker discovery. In the light of the identified gaps in our accumulated knowledge on the subject, we highlight the importance for couples seeking ART to follow the constantly revised guidelines and the need of specific ZIKV diagnosis tools for semen screening to contain ZIKV virus spread and make ART safer.

Spatial modelling of the infestation indices of Aedes aegypti: an innovative strategy for vector control actions in developing countries

“…Other studies conducted in Taiwan, Sri Lanka and Vietnam [13,14,29] have shown that larval indices may be closely related to the incidence of dengue epidemics and arboviruses. In Brazil, similar research was conducted in Rio de Janeiro, São Paulo and Maranhão [14,18,19]. These studies used the infestation index in isolation; this differs from the present study which shows that patterns of spatial distribution and risk levels from small territorial units of analysis (census tracts, for example), can indicate that these risks can be connected into larger units, especially amongst adjoining neighbourhoods.…”

“…The team from Tahiti (French Polynesia) had played in the Pernambuco Arena in June 2013 and the viral phylogenetic study showed that the origin of the Brazilian strain was Asian, sharing a common ancestor circulating in French Polynesia [18]. The Zika virus may have probably been introduced in Pernambuco, which could explain the larger size of the epidemic in this state and neighbouring areas, such as Campina Grande [19]. Zika virus was associated with a high prevalence of cases of congenital syndrome Zika, which has led the country to an emergency public health situation [20].…”

Matrix metalloproteinase 9 facilitates Zika virus invasion of the testis by modulating the integrity of the blood-testis barrier

“…In these models, ZIKV infects and replicates in a variety of testicular cell types, including interstitial Leydig cells, Sertoli cells (SCs), and germ cells, and can cause testicular damage and reduction in motile sperms, resulting in infertility in male mice [16,17,19]. Several reports have revealed that SCs, which constitute the BTB, are highly susceptible to ZIKV infection, likely because they express high levels of AXL [23], a host molecule reported to be a possible attachment receptor or key factor promoting ZIKV infection [24]. Thus, SCs may act as a reservoir for long-term replication of virus in the testes, allowing ZIKV to continually infect germ cells and developing spermatocytes, even after peripheral clearance [25].…”

“…Thus, SCs may act as a reservoir for long-term replication of virus in the testes, allowing ZIKV to continually infect germ cells and developing spermatocytes, even after peripheral clearance [25]. Recent studies have shown that ZIKV RNA can persist in human male semen up to 188 days after the onset of infection [23] illustrating its ability to pass through the BTB and disseminate into male reproductive tract [26]. Moreover, Govero et al also found that the prolongation of ZIKV infection is accompanied by the loss of BTB integrity [16].…”

Zika Virus in Africa: Epidemiology and Determinants

“…The virus is also present in urine samples of ZIKV patients even after the onset of symptoms. Current evidence suggests that kidney tissue is a suitable environment for the replication of the virus [66,67].…”