In vitro and in vivo co-infection and super-infection dynamics of Mayaro and Zika viruses in mosquito and vertebrate backgrounds

Factors related to increasing globalization and climate change have contributed to the simultaneous increase and spread of arboviral diseases. Co-circulation of multiple arboviruses in the same geographic regions provides impetus to study the impacts of multiple arbovirus infections in a single vector. In the present study we describe co-infection and super-infection with Mayaro virus (Family Togaviridae, genus Alphavirus) and Zika virus (family Flaviviridae, genus Flavivirus) in vertebrate cells, mosquito cells, and Aedes aegypti mosquitoes to understand the interaction dynamics of these pathogens and effects on viral infection, dissemination and transmission. In Aedes aegypti mosquitoes, co-infection has a negative impact on infection and dissemination rates for Zika virus, but not Mayaro virus, when compared to single infection scenarios, and super-infection of Mayaro virus with a previous Zika virus infection resulted in increased Mayaro virus infection rates. We found that co-infection and super-infection negatively affected Zika viral replication in vertebrate cells (Vero and Huh), resulting in the complete blockage of Zika virus replication in some scenarios. At the cellular level, we demonstrate that single vertebrate and insect cells can be simultaneously infected with Zika and Mayaro viruses. This study highlights the dynamics of arboviral co- and super-infections and emphasizes the importance of considering these dynamics during risk assessment in epidemic areas.

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The P-MAPA immunomodulator partially prevents apoptosis induced by Zika virus infection in THP-1 cells

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200602140005 ◽

2020 ◽

Vol 21 ◽

Cited By ~ 1

Author(s):

Morganna C. Lima ◽

Elisa A. N. Azevedo ◽

Clarice N. L. de Morais ◽

Larissa I. O. de Sousa ◽

Bruno M. Carvalho ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Death ◽

Virus Infection ◽

Virus Replication ◽

Zika Virus ◽

Mammalian Cells ◽

Caspase 3 ◽

Neurological Complications ◽

Zika Virus Infection

Background: Zika virus is an emerging arbovirus of global importance. ZIKV infection is associated with a range of neurological complications such as the Congenital Zika Syndrome and Guillain Barré Syndrome. Despite the magnitude of recent outbreaks, there is no specific therapy to prevent or to alleviate disease pathology. Objective: To investigate the role of P-MAPA immunomodulator in Zika-infected THP-1 cells. Methods: THP-1 cells were subjected at Zika virus infection (Multiplicity of Infection = 0.5) followed by treatment with P-MAPA for until 96 hours post-infection. After that, the cell death was analyzed by annexin+/ PI+ and caspase 3/ 7+ staining by flow cytometry. In addition, the virus replication and cell proliferation were accessed by RT-qPCR and Ki67 staining, respectively. Results: We demonstrate that P-MAPA in vitro treatment significantly reduces Zika virus-induced cell death and caspase-3/7 activation on THP-1 infected cells, albeit it has no role in virus replication and cell proliferation. Conclusions: Our study reveals that P-MAPA seems to be a satisfactory alternative to inhibits the effects of Zika virus infection in mammalian cells.

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The Ability of Zika virus Intravenous Immunoglobulin to Protect From or Enhance Zika Virus Disease

Frontiers in Immunology ◽

10.3389/fimmu.2021.717425 ◽

2021 ◽

Vol 12 ◽

Author(s):

Amelia K. Pinto ◽

Mariah Hassert ◽

Xiaobing Han ◽

Douglas Barker ◽

Trevor Carnelley ◽

...

Keyword(s):

Virus Infection ◽

Polyclonal Antibody ◽

Zika Virus ◽

Virus Disease ◽

Polyclonal Antibodies ◽

Antibody Therapeutics ◽

The World ◽

Flavivirus Infection

The closely related flaviviruses, dengue and Zika, cause significant human disease throughout the world. While cross-reactive antibodies have been demonstrated to have the capacity to potentiate disease or mediate protection during flavivirus infection, the mechanisms responsible for this dichotomy are still poorly understood. To understand how the human polyclonal antibody response can protect against, and potentiate the disease in the context of dengue and Zika virus infection we used intravenous hyperimmunoglobulin (IVIG) preparations in a mouse model of the disease. Three IVIGs (ZIKV-IG, Control-Ig and Gamunex®) were evaluated for their ability to neutralize and/or enhance Zika, dengue 2 and 3 viruses in vitro. The balance between virus neutralization and enhancement provided by the in vitro neutralization data was used to predict the IVIG concentrations which could protect or enhance Zika, and dengue 2 disease in vivo. Using this approach, we were able to define the unique in vivo dynamics of complex polyclonal antibodies, allowing for both enhancement and protection from flavivirus infection. Our results provide a novel understanding of how polyclonal antibodies interact with viruses with implications for the use of polyclonal antibody therapeutics and the development and evaluation of the next generation flavivirus vaccines.

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Experimental Zika virus infection in Aedes aegypti: Susceptibility, transmission & co-infection with dengue & chikungunya viruses

The Indian Journal of Medical Research ◽

10.4103/ijmr.ijmr_1142_17 ◽

2018 ◽

Vol 147 (1) ◽

pp. 88 ◽

Cited By ~ 7

Author(s):

DevendraT Mourya ◽

MangeshD Gokhale ◽

TriparnaD Majumdar ◽

PragyaD Yadav ◽

Vimal Kumar ◽

...

Keyword(s):

Virus Infection ◽

Aedes Aegypti ◽

Zika Virus ◽

Zika Virus Infection

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Autophagy Contributes to Host Immunity and Protection against Zika Virus Infection via Type I IFN Signaling

Mediators of Inflammation ◽

10.1155/2020/9527147 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Yuyi Huang ◽

Yujie Wang ◽

Shuhui Meng ◽

Zhuohang Chen ◽

Haifan Kong ◽

...

Keyword(s):

Virus Infection ◽

Cell Line ◽

Zika Virus ◽

Fetal Brain ◽

Host Immunity ◽

Type I ◽

Type I Ifn ◽

Zikv Infection

Recent studies have indicated that the Zika virus (ZIKV) has a significant impact on the fetal brain, and autophagy is contributing to host immune response and defense against virus infection. Here, we demonstrate that ZIKV infection triggered increased LC3 punctuation in mouse monocyte-macrophage cell line (RAW264.7), mouse microglial cell line (BV2), and hindbrain tissues, proving the occurrence of autophagy both in vitro and in vivo. Interestingly, manual intervention of autophagy, like deficiency inhibited by 3-MA, can reduce viral clearance in RAW264.7 cells upon ZIKV infection. Besides, specific siRNA strategy confirmed that autophagy can be activated through Atg7-Atg5 and type I IFN signaling pathway upon ZIKV infection, while knocking down of Atg7 and Atg5 effectively decreased the ZIKV clearance in phagocytes. Furthermore, we analyzed that type I IFN signaling could contribute to autophagic clearance of invaded ZIKV in phagocytes. Taken together, our findings demonstrate that ZIKV-induced autophagy is favorable to activate host immunity, particularly through type I IFN signaling, which participates in host protection and defense against ZIKV infection.

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JMX0207, a Niclosamide Derivative with Improved Pharmacokinetics, Suppresses Zika Virus Infection Both In Vitro and In Vivo

ACS Infectious Diseases ◽

10.1021/acsinfecdis.0c00217 ◽

2020 ◽

Vol 6 (10) ◽

pp. 2616-2628 ◽

Cited By ~ 1

Author(s):

Zhong Li ◽

Jimin Xu ◽

Yuekun Lang ◽

Xiaoyu Fan ◽

Lili Kuo ◽

...

Keyword(s):

Virus Infection ◽

Zika Virus ◽

Zika Virus Infection

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Different populations of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) from Central Africa are susceptible to Zika virus infection

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008163 ◽

2020 ◽

Vol 14 (3) ◽

pp. e0008163 ◽

Cited By ~ 5

Author(s):

Basile Kamgang ◽

Marie Vazeille ◽

Armel Tedjou ◽

Aurélie P. Yougang ◽

Theodel A. Wilson-Bahun ◽

...

Keyword(s):

Virus Infection ◽

Aedes Aegypti ◽

Aedes Albopictus ◽

Zika Virus ◽

Central Africa ◽

Zika Virus Infection ◽

Different Populations

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Embryotoxic impact of Zika virus in a rhesus macaque in vitro implantation model†

Biology of Reproduction ◽

10.1093/biolre/ioz236 ◽

2020 ◽

Vol 102 (4) ◽

pp. 806-816 ◽

Cited By ~ 4

Author(s):

Lindsey N Block ◽

Matthew T Aliota ◽

Thomas C Friedrich ◽

Michele L Schotzko ◽

Katherine D Mean ◽

...

Keyword(s):

Rhesus Macaque ◽

Pregnancy Outcomes ◽

Zika Virus ◽

Negative Impact ◽

Culture Media ◽

Blastocyst Formation ◽

Placental Development ◽

Zikv Infection ◽

The Impact

Abstract Zika virus (ZIKV) infection is associated with adverse pregnancy outcomes in humans, and infection in the first trimester can lead to miscarriage and stillbirth. Vertical and sexual transmissions of ZIKV have been demonstrated, yet the impact of infection during the initial stages of pregnancy remains unexplored. Here we defined the impact of ZIKV on early embryonic and placental development with a rhesus macaque model. During in vitro fertilization (IVF), macaque gametes were inoculated with a physiologically relevant dose of 5.48log10 plaque-forming units (PFU) of Zika virus/H.sapiens-tc/PUR/2015/PRVABC59_v3c2. Exposure at fertilization did not alter blastocyst formation rates compared to controls. To determine the impact of ZIKV exposure at implantation, hatched blastocysts were incubated with 3.26log10, 4.26log10, or 5.26log10 PFU, or not exposed to ZIKV, followed by extended embryo culture for 10 days. ZIKV exposure negatively impacted attachment, growth, and survival in comparison to controls, with exposure to 5.26log10 PFU ZIKV resulting in embryonic degeneration by day 2. Embryonic secretion of pregnancy hormones was lower in ZIKV-exposed embryos. Increasing levels of infectious virus were detected in the culture media post-exposure, suggesting that the trophectoderm is susceptible to productive ZIKV infection. These results demonstrate that ZIKV exposure severely impacts the zona-free blastocyst, whereas exposure at the time of fertilization does not hinder blastocyst formation. Overall, early stages of pregnancy may be profoundly sensitive to infection and pregnancy loss, and the negative impact of ZIKV infection on pregnancy outcomes may be underestimated.

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MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0006154 ◽

2018 ◽

Vol 12 (1) ◽

pp. e0006154 ◽

Cited By ~ 21

Author(s):

Dominic Paquin-Proulx ◽

Vivian I. Avelino-Silva ◽

Bianca A. N. Santos ◽

Nathália Silveira Barsotti ◽

Fabiana Siroma ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Zika Virus ◽

Dengue Virus Infection ◽

Mait Cells ◽

Zika Virus Infection

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Zika virus infection drives epigenetic modulation of immunity by the histone acetyltransferase CBP of Aedes aegypti

10.1101/2021.10.22.463187 ◽

2021 ◽

Author(s):

Anderson de Mendonca Amarante ◽

Isabel Caetano de Abreu da Silva ◽

Amanda Roberta Revoredo Vicentino ◽

Vitor Coutinho Carneiro ◽

Marcia de Amorim Pinto ◽

...

Keyword(s):

Virus Infection ◽

Aedes Aegypti ◽

Zika Virus ◽

Histone Deacetylases ◽

Histone Acetyltransferase ◽

Fat Body ◽

Survival Rates ◽

Immune Genes ◽

Wide Range

Epigenetic mechanisms are responsible for a wide range of biological phenomena in insects, controlling embryonic development, growth, aging and nutrition. Despite this, the role of epigenetics in shaping insect-pathogen interactions has received little attention. Gene expression in eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we explored the role of the Aedes aegypti histone acetyltransferase CBP (AaCBP) after infection with Zika virus, focusing on the two main immune tissues, the midgut and fat body. We showed that the expression and activity of AaCBP could be positively modulated by blood meal and Zika infection. Nevertheless, Zika-infected mosquitoes that were silenced for AaCBP revealed a significant reduction in the acetylation of H3K27 (CBP target-marker), followed by downmodulation of the expression of immune genes, higher titers of Zika virus and lower survival rates. Importantly, in Zika-infected mosquitoes that were treated with sodium butyrate, a histone deacetylase inhibitor, their capacity to fight virus infection was rescued. Our data point to a direct correlation among histone hyperacetylation by AaCBP, upregulation of antimicrobial peptide genes and increased survival of Zika-infected-A. aegypti.

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