Biology subjects

Gavino-Leopoldino, D.

Publications and source records attributed to Gavino-Leopoldino, D..

3 recordsLinked to original sources

bioRxiv2022

Different outcomes of neonatal and adult Zika virus infection on startle reflex and prepulse inhibition in mice

Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the motor, sensorial and cognitive impairments observed in ZIKV-infected patients. However, to date, no startle response or prepulse inhibition (PPI) assessment has been made in patients or animal models. In this study, we identified different outcomes for the age of infection and sex in wild-type mice: neonatally infected animals presented an increase in PPI and startle latency in both sexes, while adult infected males presented lower startle amplitude but preserved PPI. Our data further the understanding of the functional impacts of ZIKV on the developing and mature nervous system, which could help explain other behavioral and cognitive alterations caused by the virus. With this study, we support the use of startle reflex testing in ZIKV exposed patients, especially infants, allowing for early detection of functional neuromotor damage and early intervention.

neuroscience↗

bioRxiv2020

Zika virus replicates in skeletal muscle contributing to peripheral viral amplification prior to reach neural tissue

Zika virus (ZIKV) infections are still a worldwide concern due to the severity of neurological outcomes. ZIKV neurotropism is well characterized, but peripheral tissue could be sites of viral amplification, contributing to endothelial-barrier crossing and access to peripheral nerves. During acute and late phases of infection, ZIKV can be detected in several body fluids, eyes, testis and vagina. However, the importance of initial replication sites for the establishment of infection and viral spread remain unknown. Here we demonstrated that ZIKV replicates primarily in human muscle precursor cells, resulting in cell death and inhibition of myogenesis. ZIKV also replicates in fetal muscle after maternal transmission and in infected neonate mice, inducing lesions and inflammation. Muscle was an important site of viral amplification, sustaining higher peripheral viral loads than liver and spleen. In addition, ZIKV showed rapid and sustained replication kinetics in muscle even before replication in the neural tissues, persisting until 16 days post infection. Our results highlight the importance of muscle in ZIKV pathogenesis as a peripheral site of viral amplification which may contribute to ZIKV reaching neural structures. Author SummaryZika Virus (ZIKV) neurotropism and its deleterious effects on central nervous system have been well characterized. But, investigations of the initial replication sites for the establishment of infection and viral spread to neural tissues remain under explored. Here we demonstrated that ZIKV replicates primarily in human skeletal muscle precursor cells, resulting in cell death and disrupted myogenesis. ZIKV also replicates in muscle of fetus and neonate mice inducing muscle damage and inflammation. Muscle replication occurs before amplification in peripheral nerves and brain, contributing to the increase of peripheral ZIKV load and dissemination. In addition, ZIKV RNA still been detected in skeletal muscle at late stages of infection. Overall, our findings showed that skeletal muscle is involved in ZIKV pathogenesis, contributing to a broader understanding of ZIKV infection. Thus, opens new aspects in the investigation of the long-term consequence of early infection.

microbiology↗

bioRxiv2019

Mayaro virus replication restriction and induction of muscular inflammation in mice are dependent on age and type-I interferon response

Mayaro virus (MAYV) is an emergent Arbovirus belonging to the Alphavirus genus from the Togaviridae family which has been circulated in forest regions of American continent through small outbreaks. Recent studies warned for the risk of MAYV dispersion to new areas and for the potential establishment of an urban epidemic cycle. Similar to Chikungunya and other arthritogenic Alphavirus, MAYV-induced disease shows a high prevalence of arthralgia and myalgia that can persist for months. Despite this, knowledge regarding pathogenesis, characteristics of host immune response, and resolution of MAYV infections are still limited. Here we investigated the dependence of age, innate and adaptive immunity for the control of MAYV replication and induction of inflammation in mice. We observed that age and type I interferon response are related to restriction of MAYV infection and tissue inflammation in mice. Moreover, we showed that MAYV continues to replicate persistently in adult recombination activation gene-1 efficient mice (RAG1-/-), indicating that adaptive immunity is essential to MAYV clearance. Despite chronic replication, infected adult RAG1-/- mice did not develop an apparent signal of muscle damage at late infection. On the other hand, MAYV infection induces muscular and paw inflammation in young WT and adult Type I Interferon receptor deficient mice (IFNAR-/-). In addition, MAYV infection triggers an increase in the expression of pro-inflammatory mediators, such as TNF, IL-6, KC, IL-1{beta}, MCP-1, and RANTES, in muscle tissue, and decreases TGF-{beta} expression. Taken together, our study contributes to the comprehension of MAYV pathogenesis, and describes a translational mouse model for further studies of MAYV infection, as well for testing vaccine and therapeutic strategies against this virus.\n\nAuthor SummaryMAYV-induced disease presents a high prevalence of arthralgia and myalgia that potentially persist for months, which is characteristic of the arthritogenic Alphavirus group. However, information regarding MAYV infection and the molecular mechanism of pathogenesis is still scarce. Here we investigated the dependence of age, innate and adaptive immunity for the control of MAYV replication and induction of inflammation in mice. We observed that tissue inflammation and the restriction of MAYV replication in mice are affected by aging and type I interferon response. Besides, we also showed that adaptive immunity was important for MAYV clearance in adult mice. Histological analyses demonstrated that MAYV replication triggered muscular and paw inflammation in young WT and adult type-I interferon receptor deficient mice. In addition, the level of expression of several pro-inflammatory cytokines was increased in the muscle MAYV-infected mice. Our data provide an advance for understanding the molecular mechanism involved in MAYV pathogenesis, as well as describes an in vivo model for further investigations on MAYV infection and for antiviral compounds and vaccine testing.

microbiology↗