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1.
Virology ; 543: 34-42, 2020 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-32056845

RESUMEN

Zika Virus (ZIKV) is a Flavivirus transmitted primarily via the bite of infected Aedes aegypti mosquitoes. Globally, 87 countries and territories have recorded autochthonous mosquito-borne transmission of ZIKV as at July 2019 and distributed across four of the six WHO Regions. Outbreaks of ZIKV infection peaked in 2016 and declined substantially throughout 2017 and 2018 in the Americas region. There is the likely risk for ZIKV to spread to more countries. There is also the potential for the re-emergence of ZIKV in all places with prior reports of the virus transmission. The current status of ZIKV transmission and spread is, however, a global health threat, and from the aforementioned, has the potential to re-emerge as an epidemic. This review summarizes the past and present spread of ZIKV outbreak-2007-2019, the genome, transmission cycle, clinical manifestations, vaccine and antiviral drug advancement.

2.
Cells ; 9(1)2020 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-31947958

RESUMEN

To date, no safe vaccine or antivirals for Zika virus (ZIKV) infection have been found. The pathogenesis of severe Zika, where host and viral factors participate, remains unclear. For the control of Zika, it is important to understand how ZIKV interacts with different host cells. Knowledge of the targeted cellular pathways which allow ZIKV to productively replicate and/or establish prolonged viral persistence contributes to novel vaccines and therapies. Monocytes and endothelial vascular cells are the main ZIKV targets. During the infection process, cells are capable of releasing extracellular vesicles (EVs). EVs are mediators of intercellular communication. We found that mosquito EVs released from ZIKV-infected (C6/36) cells carry viral RNA and ZIKV-E protein and are able to infect and activate naïve mosquito and mammalian cells. ZIKV C6/36 EVs promote the differentiation of naïve monocytes and induce a pro-inflammatory state with tumor necrosis factor-alpha (TNF-α) mRNA expression. ZIKV C6/36 EVs participate in endothelial vascular cell damage by inducing coagulation (TF) and inflammation (PAR-1) receptors at the endothelial surface of the cell membranes and promote a pro-inflammatory state with increased endothelial permeability. These data suggest that ZIKV C6/36 EVs may contribute to the pathogenesis of ZIKV infection in human hosts.

3.
Nat Commun ; 11(1): 260, 2020 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-31937766

RESUMEN

Transmission from an infected mosquito to a host is an essential process in the life cycle of mosquito-borne flaviviruses. Numerous studies have demonstrated that mosquito saliva facilitates viral transmission. Here we find that a saliva-specific protein, named Aedes aegypti venom allergen-1 (AaVA-1), promotes dengue and Zika virus transmission by activating autophagy in host immune cells of the monocyte lineage. The AG6 mice (ifnar1-/-ifngr1-/-) bitten by the virus-infected AaVA-1-deficient mosquitoes present a lower viremia and prolonged survival. AaVA-1 intracellularly interacts with a dominant negative binder of Beclin-1, known as leucine-rich pentatricopeptide repeat-containing protein (LRPPRC), and releases Beclin-1 from LRPPRC-mediated sequestration, thereby enabling the initialization of downstream autophagic signaling. A deficiency in Beclin-1 reduces viral infection in mice and abolishes AaVA-1-mediated enhancement of ZIKV transmission by mosquitoes. Our study provides a mechanistic insight into saliva-aided viral transmission and could offer a potential prophylactic target for reducing flavivirus transmission.

4.
Artículo en Inglés | MEDLINE | ID: mdl-31934825

RESUMEN

Zika virus (ZIKV) is an emerging mosquito-borne pathogen belonging to the genus Flavivirus of the family Flaviviridae. Aedes albopictus is widely distributed in China. However, little is known about the vector competence of Ae. albopictus in China. The present study presents the oral susceptibility and vector competence of Ae. albopictus Guangzhou strain to ZIKV. Additionally, vertical transmission of ZIKV is described. The results demonstrated the susceptibility of local Ae. albopictus mosquitoes to ZIKV with an extrinsic incubation period of 6 days. Disseminated infection was observed in Ae. albopictus starting on day 2 postinfection (PI). Starting on day 6 PI, the saliva of Ae. albopictus exhibited ZIKV infection, and the transmission rate was 36.4%. Vertical transmission was observed during the first gonotrophic cycle. The minimum infection rate was observed in third-to-fourth instar larvae.

5.
Nat Microbiol ; 5(2): 239-247, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31819213

RESUMEN

The recent Zika virus (ZIKV) and chikungunya virus epidemics highlight the explosive nature of arthropod-borne viruses (arboviruses) transmitted by Aedes spp. mosquitoes1,2. Vector competence and the extrinsic incubation period (EIP) are two key entomological parameters used to assess the public health risk posed by arboviruses3. These are typically measured empirically by offering mosquitoes an infectious blood meal and temporally sampling mosquitoes to determine the infection and transmission status. This approach has been used for the better part of a century; however, it does not accurately capture the biology and behaviour of many mosquito vectors that refeed frequently (every 2-3 d)4. Here, we demonstrate that acquisition of a second non-infectious blood meal significantly shortens the EIP of ZIKV-infected Aedes aegypti by enhancing virus dissemination from the mosquito midgut. Similarly, a second blood meal increases the competence of this species for dengue virus and chikungunya virus as well as Aedes albopictus for ZIKV, suggesting that this phenomenon may be common among other virus-vector pairings and that A. albopictus might be a more important vector than once thought. Blood-meal-induced microperforations in the virus-impenetrable basal lamina that surrounds the midgut provide a mechanism for enhanced virus escape. Modelling of these findings reveals that a shortened EIP would result in a significant increase in the basic reproductive number, R0, estimated from experimental data. This helps to explain how A. aegypti can sustain explosive epidemics such as ZIKV despite relatively poor vector competence in single-feed laboratory trials. Together, these data demonstrate a direct and unrecognized link between mosquito feeding behaviour, EIP and vector competence.

6.
Nat Commun ; 10(1): 5677, 2019 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-31831806

RESUMEN

An important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses of pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking. Here we report maternal vaccination using a live-attenuated ZIKV vaccine (3'UTR-∆10-LAV) in a pregnant mouse model. Maternal immunization with 3'UTR-∆10-LAV does not cause any adverse effects on pregnancy, fetal development, or offspring behavior. One maternal immunization fully protects dams against ZIKV infection and in utero transmission. Although neutralizing antibody alone is sufficient to prevent in utero transmission, a higher neutralizing titer is required to protect pregnant mice against in utero transmission than that required to protect non-pregnant mice against viral infection. The immunized dams transfer maternal antibodies to pups, which protect neonates against ZIKV infection. Notably, pregnancy weakens maternal T cell response to 3'UTR-∆10-LAV vaccination. Our results suggest that, besides vaccinating non-pregnant individuals, 3'UTR-∆10-LAV may also be considered for maternal vaccination.

7.
Nat Commun ; 10(1): 5730, 2019 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-31844054

RESUMEN

In 2015 and 2016, Zika virus (ZIKV) swept through dengue virus (DENV) endemic areas of Latin America. These viruses are of the same family, share a vector and may interact competitively or synergistically through human immune responses. We examine dengue incidence from Brazil and Colombia before, during, and after the Zika epidemic. We find evidence that dengue incidence was atypically low in 2017 in both countries. We investigate whether subnational Zika incidence is associated with changes in dengue incidence and find mixed results. Using simulations with multiple assumptions of interactions between DENV and ZIKV, we find cross-protection suppresses incidence of dengue following Zika outbreaks and low periods of dengue incidence are followed by resurgence. Our simulations suggest correlations in DENV and ZIKV reproduction numbers could complicate associations between ZIKV incidence and post-ZIKV DENV incidence and that periods of low dengue incidence are followed by large increases in dengue incidence.

8.
PLoS Negl Trop Dis ; 13(12): e0007988, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31877132

RESUMEN

BACKGROUND: Detecting and monitoring the transmission of arboviruses such as Zika virus (ZIKV), dengue virus, and chikungunya virus is critical for prevention and control activities. Previous work has compared the ability of different human-focused surveillance strategies to detect ZIKV transmission in U.S. counties where no known transmission had occurred, but whether virological surveillance in mosquitoes could represent an effective surveillance system is unclear. OBJECTIVES: We leveraged a unique set of data from human and virological surveillance in Ae. aegypti during the 2016 ZIKV epidemic in Caguas, Puerto Rico, to compare alternative strategies for detecting and monitoring ZIKV activity. METHODS: We developed a simulation model for mosquito and human surveillance strategies and simulated different transmission scenarios with varying infection rates and mosquito trap densities. We then calculated the expected weekly number of detected infections, the probability of detecting transmission, and the number of tests needed and compared the simulations with observed data from Caguas. RESULTS: In simulated high transmission scenarios (1 infection per 1,000 people per week), the models demonstrated that both approaches had estimated probabilities of detection of greater than 78%. In simulated low incidence scenarios, vector surveillance had higher sensitivity than human surveillance and sensitivity increased with more traps, more trapping effort, and testing. In contrast, the actual data from Caguas indicated that human virological surveillance was more sensitive than vector virological surveillance during periods of both high and low transmission. CONCLUSION: In scenarios where human surveillance is not possible or when transmission intensity is very low, virological surveillance in Ae. aegypti may be able to detect and monitor ZIKV epidemic activity. However, surveillance for humans seeking care for Zika-like symptoms likely provides an equivalent or more sensitive indicator of transmission intensity in most circumstances.

9.
Sci Rep ; 9(1): 17852, 2019 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-31780744

RESUMEN

Arboviral diseases such as chikungunya, dengue, and Zika viruses have been threatening the European countries since the introduction in 1979 of the major vector Aedes albopictus. In 2017, more than three hundred of CHIKV autochthonous cases were reported in Italy, highlighting the urgent need for a risk assessment of arboviral diseases in European countries. In this study, the vector competence for three major arboviruses were analyzed in eight Ae. albopictus populations from Europe. Here we show that Southern European Ae. albopictus were susceptible to CHIKV, DENV-1 and ZIKV with the highest vector competence for CHIKV. Based on vector competence data and vector distribution, a prediction risk map for CHIKV was generated stressing the fear of CHIKV and to a lesser extent, of other arboviruses for Europe, calling us for new public health strategies.

10.
Viruses ; 11(11)2019 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-31752097

RESUMEN

Evolutionary theory indicates that virus virulence is shaped by a trade-off between instantaneous rate of transmission and duration of infection. For most viruses, infection is curtailed by immune clearance, but there are few empirical tests of the transmission-clearance trade-off hypothesis. We exposed A129 mice to bites from groups of 1, 2-4, or 6-9 Aedes albopictus mosquitoes infected with Zika virus (ZIKV). We predicted that a higher number of infectious mosquito bites would deliver a higher total dose of the virus, and that increasing dose would result in earlier onset, higher magnitude, and shorter duration of viremia, as well as a more robust neutralizing antibody response. We found that increases in the number of mosquito bites delivered resulted in significantly different virus replication dynamics with higher, earlier peak titers. All mice experienced a transient weight loss following infection, but the nadir in weight loss was delayed in the mice that received the highest number of bites. Viremia persisted past the period of measurement in this study, so we did not capture its duration. However, the association at the level of the individual mouse between the estimated virus dose delivered and neutralizing antibody titer was remarkably strong, supporting the transmission-clearance trade-off hypothesis.

11.
Int J Infect Dis ; 91: 38-43, 2019 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-31704226

RESUMEN

OBJECTIVE: To evaluate the diagnostic performance of the Inbios (Seattle, US) and Euroimmun (Luebeck, Germany) chikungunya virus (CHIKV) IgM enzyme-linked immunoassays (ELISAs). METHODS: We evaluated the tests' accuracy on sera from 372 patients enrolled in an acute febrile illness surveillance study performed in Salvador, Brazil from Sept/2014 to Jul/2016, a period of simultaneous CHIKV, dengue (DENV), and Zika (ZIKV) virus transmission. We assessed the sensitivity on acute and paired convalescent sera from RT-PCR-confirmed CHIKV cases (collected at median one and 19 days post-onset of symptoms, respectively), and the specificity on sera of RT-PCR-confirmed DENV and ZIKV cases, and on negative patients. RESULTS: The Inbios and Euroimmun tests' sensitivities for acute samples were 4.0% and 10.3%, while for convalescent samples they were 92.4% and 96.9%, respectively. Overall, Inbios IgM ELISA specificities for acute and convalescent samples were 97.7% and 90.5%, respectively, and Euroimmun specificities were 88.5% and 83.9%, respectively. CONCLUSIONS: Both tests presented high sensitivity for convalescent samples. However, the Euroimmun test returned more equivocal results and presented a slightly lower specificity, which might result in a higher rate of false positives if the test is used in scenarios of low CHIKV transmission, when the chance of CHIKV infection is lower.

12.
BMC Infect Dis ; 19(1): 963, 2019 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-31718580

RESUMEN

BACKGROUND: Colombia was the second most affected country during the American Zika virus (ZIKV) epidemic, with over 109,000 reported cases. Despite the scale of the outbreak, limited genomic sequence data were available from Colombia. We sought to sequence additional samples and use genomic epidemiology to describe ZIKV dynamics in Colombia. METHODS: We sequenced ZIKV genomes directly from clinical diagnostic specimens and infected Aedes aegypti samples selected to cover the temporal and geographic breadth of the Colombian outbreak. We performed phylogeographic analysis of these genomes, along with other publicly-available ZIKV genomes from the Americas, to estimate the frequency and timing of ZIKV introductions to Colombia. RESULTS: We attempted PCR amplification on 184 samples; 19 samples amplified sufficiently to perform sequencing. Of these, 8 samples yielded sequences with at least 50% coverage. Our phylogeographic reconstruction indicates two separate introductions of ZIKV to Colombia, one of which was previously unrecognized. We find that ZIKV was first introduced to Colombia in February 2015 (95%CI: Jan 2015 - Apr 2015), corresponding to 5 to 8 months of cryptic ZIKV transmission prior to confirmation in September 2015. Despite the presence of multiple introductions, we find that the majority of Colombian ZIKV diversity descends from a single introduction. We find evidence for movement of ZIKV from Colombia into bordering countries, including Peru, Ecuador, Panama, and Venezuela. CONCLUSIONS: Similarly to genomic epidemiological studies of ZIKV dynamics in other countries, we find that ZIKV circulated cryptically in Colombia. More accurately dating when ZIKV was circulating refines our definition of the population at risk. Additionally, our finding that the majority of ZIKV transmission within Colombia was attributable to transmission between individuals, rather than repeated travel-related importations, indicates that improved detection and control might have succeeded in limiting the scale of the outbreak within Colombia.


Asunto(s)
Genoma Viral , Infección por el Virus Zika/virología , Virus Zika/genética , Aedes/virología , Animales , Colombia/epidemiología , Brotes de Enfermedades , Evolución Molecular , Variación Genética , Humanos , Filogenia , Filogeografía , Virus Zika/clasificación , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/transmisión
13.
Euro Surveill ; 24(45)2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31718742

RESUMEN

On 1 October 2019, a locally-acquired Zika virus disease case was laboratory confirmed in Hyères, Var department. Active case finding identified two additional locally-acquired cases living within 90 m, with symptom onset 8 days before the index case. Extensive patient interviews did not yield information supporting transmission through sexual contact or substances of human origin. Vector-borne transmission by local Aedes albopictus mosquitoes is the most likely mode of transmission. Here we describe the public health response.

14.
Emerg Microbes Infect ; 8(1): 1668-1678, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31735122

RESUMEN

Since its emergence in Yap Island in 2007, Zika virus (ZIKV) has affected all continents except Europe. Despite the hundreds of cases imported to European countries from ZIKV-infested regions, no local cases have been reported in localities where the ZIKV-competent mosquito Aedes albopictus is well established. Here we analysed the vector competence of European Aedes (aegypti and albopictus) mosquitoes to different genotypes of ZIKV. We demonstrate that Ae. albopictus from France was less susceptible to the Asian ZIKV than to the African ZIKV. Critically we show that effective crossing of anatomical barriers (midgut and salivary glands) after an infectious blood meal depends on a viral load threshold to trigger: (i) viral dissemination from the midgut to infect mosquito internal organs and (ii) viral transmission from the saliva to infect a vertebrate host. A viral load in body ≥4800 viral copies triggered dissemination and ≥12,000 viral copies set out transmission. Only 27.3% and 18.2% of Ae. albopictus Montpellier mosquitoes meet respectively these two criteria. Collectively, these compelling results stress the poor ability of Ae. albopictus to sustain a local transmission of ZIKV in Europe and provide a promising tool to evaluate the risk of ZIKV transmission in future outbreaks.


Asunto(s)
Aedes/fisiología , Mosquitos Vectores/fisiología , Infección por el Virus Zika/transmisión , Virus Zika/fisiología , Aedes/genética , Aedes/virología , Animales , Europa (Continente) , Femenino , Humanos , Mosquitos Vectores/genética , Mosquitos Vectores/virología , Carga Viral , Virus Zika/genética , Infección por el Virus Zika/virología
15.
Sci Rep ; 9(1): 17055, 2019 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-31745123

RESUMEN

We establish a compartmental model to study the transmission of Zika virus disease including spread through sexual contacts and the role of asymptomatic carriers. To incorporate the impact of the seasonality of weather on the spread of Zika, we apply a nonautonomous model with time-dependent mosquito birth rate and biting rate, which allows us to explain the differing outcome of the epidemic in different countries of South America: using Latin Hypercube Sampling for fitting, we were able to reproduce the different outcomes of the disease in various countries. Sensitivity analysis shows that, although the most important factors in Zika transmission are the birth rate of mosquitoes and the transmission rate from mosquitoes to humans, spread through sexual contacts also highly contributes to the transmission of Zika virus: our study suggests that the practice of safe sex among those who have possibly contracted the disease, can significantly reduce the number of Zika cases.

16.
PeerJ ; 7: e7920, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31745446

RESUMEN

Background: Zika is of great medical relevance due to its rapid geographical spread in 2015 and 2016 in South America and its serious implications, for example, certain birth defects. Recent epidemics urgently require a better understanding of geographic patterns of the Zika virus transmission risk. This study aims to map the Zika virus transmission risk in South and Central America. We applied the maximum entropy approach, which is common for species distribution modelling, but is now also widely in use for estimating the geographical distribution of infectious diseases. Methods: As predictor variables we used a set of variables considered to be potential drivers of both direct and indirect effects on the emergence of Zika. Specifically, we considered (a) the modelled habitat suitability for the two main vector species Aedes aegypti and Ae. albopictus as a proxy of vector species distributions; (b) temperature, as it has a great influence on virus transmission; (c) commonly called evidence consensus maps (ECM) of human Zika virus infections on a regional scale as a proxy for virus distribution; (d) ECM of human dengue virus infections and, (e) as possibly relevant socio-economic factors, population density and the gross domestic product. Results: The highest values for the Zika transmission risk were modelled for the eastern coast of Brazil as well as in Central America, moderate values for the Amazon basin and low values for southern parts of South America. The following countries were modelled to be particularly affected: Brazil, Colombia, Cuba, Dominican Republic, El Salvador, Guatemala, Haiti, Honduras, Jamaica, Mexico, Puerto Rico and Venezuela. While modelled vector habitat suitability as predictor variable showed the highest contribution to the transmission risk model, temperature of the warmest quarter contributed only comparatively little. Areas with optimal temperature conditions for virus transmission overlapped only little with areas of suitable habitat conditions for the two main vector species. Instead, areas with the highest transmission risk were characterised as areas with temperatures below the optimum of the virus, but high habitat suitability modelled for the two main vector species. Conclusion: Modelling approaches can help estimating the spatial and temporal dynamics of a disease. We focused on the key drivers relevant in the Zika transmission cycle (vector, pathogen, and hosts) and integrated each single component into the model. Despite the uncertainties generally associated with modelling, the approach applied in this study can be used as a tool and assist decision making and managing the spread of Zika.

17.
PLoS Negl Trop Dis ; 13(10): e0007763, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31589611

RESUMEN

Defining cases of Zika virus (ZIKV) infection is a critical challenge for epidemiological research. Due to ZIKV's overlapping clinical features and potential immunologic cross-reactivity with other flaviviruses and the current lack of an optimal ZIKV-specific diagnostic assay, varying approaches for identifying ZIKV infections have been employed to date. This paper presents the laboratory results and diagnostic criteria developed by the Microcephaly Epidemic Research Group for defining cases of maternal ZIKV infection in a cohort of pregnant women with rash (N = 694) recruited during the declining 2015-2017 epidemic in northeast Brazil. For this investigation, we tested maternal sera for ZIKV by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Immunoglobulin (Ig) M and IgG3 enzyme-linked immunosorbent assays (ELISAs), and Plaque Reduction Neutralization Test (PRNT50). Overall, 23.8% of participants tested positive by qRT-PCR during pregnancy (range of detection: 0-72 days after rash onset). However, the inter-assay concordance was lower than expected. Among women with qRT-PCR-confirmed ZIKV and further testing, only 10.1% had positive IgM tests within 90 days of rash, and only 48.5% had ZIKV-specific PRNT50 titers ≥20 within 1 year of rash. Given the complexity of these data, we convened a panel of experts to propose an algorithm for identifying ZIKV infections in pregnancy based on all available lines of evidence. When the diagnostic algorithm was applied to the cohort, 26.9% of participants were classified as having robust evidence of a ZIKV infection during pregnancy, 4.0% as having moderate evidence, 13.3% as having limited evidence of a ZIKV infection but with uncertain timing, and 19.5% as having evidence of an unspecified flavivirus infection before or during pregnancy. Our findings suggest that integrating longitudinal data from nucleic acid and serologic testing may enhance diagnostic sensitivity and underscore the need for an on-going dialogue regarding the optimization of strategies for defining cases of ZIKV in research.

18.
Emerg Infect Dis ; 25(11): 2115-2119, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31625850

RESUMEN

We examined condom use throughout pregnancy during the Zika outbreak in Puerto Rico during 2016. Overall, <25% of women reported consistent condom use during pregnancy. However, healthcare provider counseling was associated with a 3-fold increase in consistent use, reinforcing the value of provider counseling in Zika prevention efforts.

19.
BMC Med Res Methodol ; 19(1): 200, 2019 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-31655546

RESUMEN

BACKGROUND: New emerging diseases are public health concerns in which policy makers have to make decisions in the presence of enormous uncertainty. This is an important challenge in terms of emergency preparation requiring the operation of effective surveillance systems. A key concept to investigate the dynamic of infectious diseases is the basic reproduction number. However it is difficult to be applicable in real situations due to the underlying theoretical assumptions. METHODS: In this paper we propose a robust and flexible methodology for estimating disease strength varying in space and time using an alternative measure of disease transmission within the hierarchical modeling framework. The proposed measure is also extended to allow for incorporating knowledge from related diseases to enhance performance of surveillance system. RESULTS: A simulation was conducted to examine robustness of the proposed methodology and the simulation results demonstrate that the proposed method allows robust estimation of the disease strength across simulation scenarios. A real data example is provided of an integrative application of Dengue and Zika surveillance in Thailand. The real data example also shows that combining both diseases in an integrated analysis essentially decreases variability of model fitting. CONCLUSIONS: The proposed methodology is robust in several simulated scenarios of spatiotemporal transmission force with computing flexibility and practical benefits. This development has potential for broad applicability as an alternative tool for integrated surveillance of emerging diseases such as Zika.

20.
J Virol ; 94(1)2019 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-31597777

RESUMEN

Zika virus (ZIKV) infection in pregnant women is a serious threat to the development and viability of the fetus. The primary mode of ZIKV transmission to humans is through mosquito bites, but sexual transmission has also been well documented in humans. However, little is known of the short- and long-term effects of ZIKV infection on the human male reproductive system. This study examines the effects of ZIKV infection on the male reproductive organs and semen and the immune response of the olive baboon (Papio anubis). Nine mature male baboons were infected with ZIKV (French Polynesian strain) subcutaneously. Six animals were euthanized at 41 days, while three animals were euthanized at 10 or 11 days postinfection (dpi). Viremia and clinical evidence of infection were present in all nine baboons. ZIKV RNA was present in the semen of five of nine baboons. ZIKV was present in the testes of two of three males euthanized at 10 or 11 dpi, but in none of six males at 41 dpi. Immunofluorescence of testes suggested the presence of ZIKV in sperm progenitor cells, macrophage penetration of seminiferous tubules, and increased tumor necrosis factor alpha (TNF-α), particularly in vascular walls. These data demonstrate that male olive baboons approximate the male human ZIKV response, including viremia, the adaptive immune response, and persistent ZIKV in semen. Although gross testicular pathology was not seen, the demonstrated breach of the testes-blood barrier and targeting of spermatogenic precursors suggest possible long-term implications in ZIKV-infected primates.IMPORTANCE Zika virus (ZIKV) is an emerging flavivirus spread through mosquitoes and sexual contact. ZIKV infection during pregnancy can lead to severe fetal outcomes, including miscarriage, fetal death, preterm birth, intrauterine growth restriction, and fetal microcephaly, collectively known as congenital Zika syndrome. Therefore, it is important to understand how this virus spreads, as well as the resulting pathogenesis in translational animal models that faithfully mimic ZIKV infection in humans. Such models will contribute to the future development of efficient therapeutics and prevention mechanisms. Through our previous work in olive baboons, we developed a nonhuman primate model that is permissive to ZIKV infection and transfers the virus vertically from mother to fetus, modeling human observations. The present study contributes to understanding of ZIKV infection in male baboon reproductive tissues and begins to elucidate how this may affect fertility, reproductive capacity, and sexual transmission of the virus.

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