scholarly journals Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques

2019 ◽  
Author(s):  
Meghan E. Breitbach ◽  
Christina M. Newman ◽  
Dawn M. Dudley ◽  
Laurel M. Stewart ◽  
Matthew T. Aliota ◽  
...  
Keyword(s):  
Zika Virus ◽  
Primary Infection ◽  
Rhesus Macaques ◽  
Secondary Infection ◽  
Denv Infection ◽  
The Other ◽  
Sample Type ◽  
Zikv Infection ◽  
Secondary Infections ◽  
Cynomolgus Macaques

AbstractZika virus (ZIKV) and dengue virus (DENV) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. The rapid emergence of ZIKV in the Americas in 2015 and 2016, and its recent associations with Guillain-Barré syndrome, birth defects, and fetal loss have led to the hypothesis that DENV infection induces cross-reactive antibodies that influence the severity of secondary ZIKV infections. It has also been proposed that pre-existing ZIKV immunity could affect DENV pathogenesis. We examined outcomes of secondary ZIKV infections in three rhesus and fifteen cynomolgus macaques, as well as secondary DENV-2 infections in three additional rhesus macaques up to a year post-primary ZIKV infection. Although cross-binding antibodies were detected prior to secondary infection for all animals and cross-neutralizing antibodies were detected for some animals, previous DENV or ZIKV infection had no apparent effect on the clinical course of heterotypic secondary infections in these animals. All animals had asymptomatic infections and, when compared to controls, did not have significantly perturbed hematological parameters. Rhesus macaques infected with DENV-2 approximately one year after primary ZIKV infection had higher vRNA loads in plasma when compared with serum vRNA loads from ZIKV-naive animals infected with DENV-2, but a differential effect of sample type could not be ruled out. In cynomolgus macaques, the serotype of primary DENV infection did not affect the outcome of secondary ZIKV infection.Author summaryPre-existing immunity to one of the four DENV serotypes is known to increase the risk of severe disease upon secondary infection with a different serotype. Due to the antigenic similarities between ZIKV and DENV, it has been proposed that these viruses could interact in a similar fashion. Data from in vitro experiments and murine models suggests that pre-existing immunity to one virus could either enhance or protect against infection with the other. These somewhat contradictory findings highlight the need for immune competent animal models for understanding the role of cross-reactive antibodies in flavivirus pathogenesis. We examined secondary ZIKV or DENV infections in rhesus and cynomolgus macaques that had previously been infected with the other virus. We assessed the outcomes of secondary ZIKV or DENV infections by quantifying vRNA loads, clinical and laboratory parameters, body temperature, and weight for each cohort of animals and compared them with control animals. These comparisons demonstrated that within a year of primary infection, secondary infections with either ZIKV or DENV were similar to primary infections and were not associated with enhancement or reduction in severity of disease based on the outcomes that we assessed.

scholarly journals Modelling the impact of antibody-dependent enhancement on disease severity of Zika virus and dengue virus sequential and co-infection

2020 ◽  
Vol 7 (4) ◽  
pp. 191749 ◽  
Author(s):  
Biao Tang ◽  
Yanni Xiao ◽  
Beate Sander ◽  
Manisha A. Kulkarni ◽  
RADAM-LAC Research Team ◽  
...  
Keyword(s):  
Viral Load ◽  
Dengue Virus ◽  
Zika Virus ◽  
Primary Infection ◽  
Secondary Infection ◽  
Peak Time ◽  
Virus Dynamics ◽  
Antibody Dependent Enhancement ◽  
Secondary Infections ◽  
Peak Viral Load

Human infections with viruses of the genus Flavivirus , including dengue virus (DENV) and Zika virus (ZIKV), are of increasing global importance. Owing to antibody-dependent enhancement (ADE), secondary infection with one Flavivirus following primary infection with another Flavivirus can result in a significantly larger peak viral load with a much higher risk of severe disease. Although several mathematical models have been developed to quantify the virus dynamics in the primary and secondary infections of DENV, little progress has been made regarding secondary infection of DENV after a primary infection of ZIKV, or DENV-ZIKV co-infection. Here, we address this critical gap by developing compartmental models of virus dynamics. We first fitted the models to published data on dengue viral loads of the primary and secondary infections with the observation that the primary infection reaches its peak much more gradually than the secondary infection. We then quantitatively show that ADE is the key factor determining a sharp increase/decrease of viral load near the peak time in the secondary infection. In comparison, our simulations of DENV and ZIKV co-infection (simultaneous rather than sequential) show that ADE has very limited influence on the peak DENV viral load. This indicates pre-existing immunity to ZIKV is the determinant of a high level of ADE effect. Our numerical simulations show that (i) in the absence of ADE effect, a subsequent co-infection is beneficial to the second virus; and (ii) if ADE is feasible, then a subsequent co-infection can induce greater damage to the host with a higher peak viral load and a much earlier peak time for the second virus, and for the second peak for the first virus.

scholarly journals Improved Immune Responses against Zika Virus after Sequential Dengue and Zika Virus Infection in Human

2018 ◽  
Author(s):  
Felix G. Delgado ◽  
Karina I. Torres ◽  
Jaime E. Castellanos ◽  
Consuelo Romero-Sánchez ◽  
Etienne Simon-Lorière ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Denv Infection ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses ◽  
B Cell Responses

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

scholarly journals Low Aedes aegypti Vector Competence for Zika Virus from Viremic Rhesus Macaques

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1345
Author(s):  
Rosilainy Surubi Fernandes ◽  
Mariana Rocha David ◽  
Filipe Vieira Santos De Abreu ◽  
Anielly Ferreira-de-Brito ◽  
Noemi R. Gardinali ◽  
...  
Keyword(s):  
Viral Load ◽  
Aedes Aegypti ◽  
Short Duration ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Vector Competence ◽  
Transmission Dynamics ◽  
Zikv Infection ◽  
Transmission Rates ◽  
Time Points

Despite worldwide efforts to understand the transmission dynamics of Zika virus (ZIKV), scanty evaluation has been made on the vector competence of Aedes aegypti fed directly on viremic human and non-human primates (NHPs). We blood-fed Ae. aegypti from two districts in Rio de Janeiro on six ZIKV infected pregnant rhesus macaques at several time points, half of which were treated with Sofosbuvir (SOF). Mosquitoes were analyzed for vector competence after 3, 7 and 14 days of incubation. Although viremia extended up to eight days post monkey inoculation, only mosquitoes fed on the day of the peak of viremia, recorded on day two, became infected. The influence of SOF treatment could not be assessed because the drug was administered just after mosquito feeding on day two. The global infection, dissemination and transmission rates were quite low (4.09%, 1.91% and 0.54%, respectively); no mosquito was infected when viremia was below 1.26 × 105 RNA copies/mL. In conclusion, Ae. aegypti vector competence for ZIKV from macaques is low, likely to be due to low viral load and the short duration of ZIKV viremia in primates suitable for infecting susceptible mosquitoes. If ZIKV infection in human and macaques behaves similarly, transmission of the Zika virus in nature is most strongly affected by vector density.

scholarly journals Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Carol L. Vinton ◽  
Samuel J. Magaziner ◽  
Kimberly A. Dowd ◽  
Shelly J. Robertson ◽  
Emerito Amaro-Carambot ◽  
...  
Keyword(s):  
Immune Responses ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Type I Interferons ◽  
Type I ◽  
Adaptive Immune Responses ◽  
Zikv Infection ◽  
Adaptive Immune ◽  
Immunodeficiency Virus

ABSTRACT Flaviviruses are controlled by adaptive immune responses but are exquisitely sensitive to interferon-stimulated genes (ISGs). How coinfections, particularly simian immunodeficiency viruses (SIVs), that induce robust ISG signatures influence flavivirus clearance and pathogenesis is unclear. Here, we studied how Zika virus (ZIKV) infection is modulated in SIV-infected nonhuman primates. We measured ZIKV replication, cellular ZIKV RNA levels, and immune responses in non-SIV-infected and SIV-infected rhesus macaques (RMs), which we infected with ZIKV. Coinfected animals had a 1- to 2-day delay in peak ZIKV viremia, which was 30% of that in non-SIV-infected animals. However, ZIKV viremia was significantly prolonged in SIV-positive (SIV+) RMs. ISG levels at the time of ZIKV infection were predictive for lower ZIKV viremia in the SIV+ RMs, while prolonged ZIKV viremia was associated with muted and delayed adaptive responses in SIV+ RMs. IMPORTANCE Immunocompromised individuals often become symptomatic with infections which are normally fairly asymptomatic in healthy individuals. The particular mechanisms that underlie susceptibility to coinfections in human immunodeficiency virus (HIV)-infected individuals are multifaceted. ZIKV and other flaviviruses are sensitive to neutralizing antibodies, whose production can be limited in HIV-infected individuals but are also sensitive to type I interferons, which are expressed at high levels in HIV-infected individuals. Data in this study highlight how individual components of the innate and adaptive immune responses which become perturbed in HIV-infected individuals influence ZIKV infection.

Demonstration of marmosets (Callithrix jacchus) as a non-human primate model for secondary dengue virus infection: high levels of viraemia and serotype cross-reactive antibody responses consistent with secondary infection of humans

2014 ◽  
Vol 95 (3) ◽  
pp. 591-600 ◽  
Author(s):  
Meng Ling Moi ◽  
Tomohiko Takasaki ◽  
Tsutomu Omatsu ◽  
Shinichiro Nakamura ◽  
Yuko Katakai ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Primary Infection ◽  
Secondary Infection ◽  
Denv Infection ◽  
Callithrix Jacchus ◽  
Antibody Responses ◽  
Infection Model ◽  
Primate Model ◽  
Bhk Cells ◽  
Denv Serotypes

There are four dengue virus (DENV) serotypes. Primary infection with one does not confer protective immunity against the others. We have reported previously that the marmoset (Callithrix jacchus) is a useful primary DENV infection model. It has been reported that secondary DENV infection with a heterotypic serotype induces viraemia kinetics and antibody responses that differ from those in primary infection. Thus, it is important to determine the utility of the marmoset as a model for secondary DENV infection. Marmosets were infected with heterologous DENV by secondary inoculation, and viraemia kinetics and antibody responses were analysed. The marmosets consistently developed high levels of viraemia after the secondary inoculation with heterologous DENV serotypes. IgM responses were lower compared with primary inoculation responses, whilst IgG responses were rapid and high. Neutralizing activities, which possessed serotype cross-reactive activities, were detected as early as 4 days after inoculation. In addition, infectious viraemia titres were higher when assayed with Fcγ receptor-expressing baby hamster kidney (BHK) cells than when assayed with conventional BHK cells, suggesting the presence of infectious virus–antibody immune complexes. After secondary infection with heterotypic DENV, the marmosets demonstrated viraemia kinetics, IgM and IgG responses, and high levels of serotype cross-reactive neutralizing antibody responses, all of which were consistent with secondary DENV infection in humans. The results indicate the marmoset as a useful animal for studying secondary, as well as primary, DENV infection.

scholarly journals Estimation of Dengue Virus IgM Persistence Using Regression Analysis

2011 ◽  
Vol 18 (12) ◽  
pp. 2183-2185 ◽  
Author(s):  
Harry E. Prince ◽  
Jose L. Matud
Keyword(s):  
Regression Analysis ◽  
Dengue Virus ◽  
Primary Infection ◽  
Secondary Infection ◽  
Disease Onset ◽  
Decay Rates ◽  
Point Index ◽  
Infection Group ◽  
Secondary Infections

ABSTRACTDengue virus IgM persistence was estimated using follow-up sera from 98 patients (60 with primary infections and 38 with secondary infections) whose first-specimen IgM index was strongly positive, suggesting recent disease onset. Regression analysis of the follow-up IgM index versus days between samples yielded a trend line that reached the cut-point index (1.10) at 179 days for the primary infection group and 139 days for the secondary infection group. This difference reflected significantly higher first-sample IgM indices in primary infections than in secondary infections rather than differences in IgM decay rates.

Strongyloides ratti: 1. Parasitological observations on primary and secondary infections in the small intestine of rats

1977 ◽  
Vol 51 (4) ◽  
pp. 301-308 ◽  
Author(s):  
R. Moqbel ◽  
D. A. Denham
Keyword(s):  
Small Intestine ◽  
Primary Infection ◽  
Secondary Infection ◽  
Secondary Infections

ABSTRACTAdult Strongyloides ratti were expelled from the small intestine of rats starting 14—18 days after a primary infection. In a secondary infection very few adult worms developed and most of these were expelled before day 14. At the time of expulsion the worms migrated posteriorly in the intestine and their size decreased.

scholarly journals Prior dengue immunity enhances Zika virus infection of the maternal-fetal interface in rhesus macaques

2021 ◽  
Author(s):  
C. M. Crooks ◽  
A. M. Weiler ◽  
S. L. Rybarczyk ◽  
M. I. Bliss ◽  
A. S. Jaeger ◽  
...  
Keyword(s):  
Zika Virus ◽  
Rhesus Macaques ◽  
Maternal Plasma ◽  
Adverse Outcomes ◽  
Zikv Infection ◽  
Primate Model ◽  
Denv Serotypes ◽  
The Impact ◽  
Human Primate ◽  
Maternal Fetal Interface

ABSTRACTConcerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that prior DENV-2 exposure enhanced ZIKV infection of maternal-fetal interface tissues in macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

scholarly journals Zika virus infection during pregnancy protects against secondary infection in the absence of CD8+ cells

2020 ◽  
Author(s):  
Blake Schouest ◽  
Margaret H. Gilbert ◽  
Rudolf P Bohm ◽  
Faith Schiro ◽  
Pyone P. Aye ◽  
...  
Keyword(s):  
Zika Virus ◽  
Immune Modulation ◽  
Secondary Infection ◽  
Zikv Infection ◽  
Cd8 Cells ◽  
Adaptive Immune ◽  
Secondary Challenge ◽  
Adaptive Immune Cells ◽  
Cell Immunity ◽  
Humoral Responses

AbstractWhile T cell immunity is an important component of the immune response to Zika virus (ZIKV) infection generally, the efficacy of these responses during pregnancy remains unknown. Here, we tested the capacity of CD8 lymphocytes to protect from secondary challenge in four macaques, two of which were depleted of CD8+ cells prior to rechallenge with a heterologous ZIKV isolate. The initial challenge during pregnancy produced transcriptional signatures suggesting complex patterns of immune modulation, but all animals efficiently controlled the rechallenge virus, implying that the primary infection conferred adequate protection. The secondary challenge promoted humoral responses and activation of innate and adaptive immune cells, suggesting a brief period of infection prior to clearance. These data confirm that ZIKV infection during pregnancy induces sufficient immunity to protect from a secondary challenge and suggest that this protection is not solely dependent on CD8 T cells but entails multiple arms of the immune system.

scholarly journals Enhancement of Zika virus infection by antibodies from West Nile virus seropositive individuals with no history of clinical infection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Himanshu Garg ◽  
Rose Yeh ◽  
Douglas M. Watts ◽  
Tugba Mehmetoglu-Gurbuz ◽  
Robert Resendes ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Zika Virus ◽  
Human Subjects ◽  
Denv Infection ◽  
Serum Samples ◽  
Endemic Region ◽  
West Nile ◽  
Zikv Infection ◽  
Antigenic Relatedness

Abstract Background Recent outbreaks of Zika Virus (ZIKV) infection and associated microcephaly has raised multiple scientific questions. The close antigenic relatedness between flaviviruses makes diagnosis of specific infection difficult. This relatedness also raises the potential of Antibody Dependent Enhancement (ADE) via cross reactive antibodies to flaviviruses like West Nile Virus (WNV) and Dengue Virus (DENV). Asymptomatic WNV infections are endemic throughout the US creating a large proportion of the population that is seropositive for WNV antibodies. Whether these sero-positive individuals potentially carry ZIKV enhancing antibodies remains unknown. Results Serum samples obtained from human subjects with symptomatic or asymptomatic WNV infection from a WNV endemic region in Texas were tested for their ability to enhance or neutralize ZIKV infection. Sero-surveillance data demonstrated a ~ 7% prevalence for WNV antibodies in the population. Sera from both symptomatic and asymptomatic WNV seropositive donors effectively neutralized WNV and to some extent DENV infection. Interestingly, WNV+ sera failed to inhibit ZIKV while significantly enhancing infection. Conversely, ZIKV specific sera effectively neutralized ZIKV, with ADE only evident at lower concentrations. The enhancement of ZIKV via WNV antibody positive sera was likely due to non-neutralizing Envelope (E) antibodies as seen with monoclonal ZIKV E antibodies. Conclusions Overall, our findings suggest that WNV antibodies in the sera significantly enhance ZIKV infection in Fc receptor positive cells with limited neutralization activity. Further studies in more relevant models of ADE will be needed to confirm the relevance of these findings in vivo.

Sign in / Sign up

Export Citation Format

Share Document