Biology subjects

Bonaldo, M. C.

Publications and source records attributed to Bonaldo, M. C..

5 recordsLinked to original sources

bioRxiv2022

Therapeutic neutralizing monoclonal antibody administration protects against lethal viscerotropic Yellow Fever infection

Few countermeasures to treat Yellow Fever virus (YFV) infection are under development, because vaccines have helped to limit new infections. Unfortunately, vaccine hesitancy, supply deficits, and a paucity of therapeutic options have left individuals at risk. Here, we tested potent YFV-specific neutralizing monoclonal antibodies in rodents and non-human primates. We administered antibodies during acute pathogenic YFV infection and demonstrate that we can prevent severe disease and death. Given the severity of YFV-induced disease, our results show that these antibodies could be effective in saving lives and fill a much-needed void in managing Yellow Fever cases during outbreaks around the world. One Sentence SummaryTherapeutic monoclonal antibodies prevent death from YFV infection.

immunology↗

bioRxiv2021

Genotype-specific Features Reduce the Susceptibility of South American Yellow Fever Virus Strains to Vaccine-Induced Antibodies

The resurgence of yellow fever in South America has prompted mitigation through vaccination against the etiologic agent, yellow fever virus (YFV). Current vaccines are based on a virulent African isolate, and their capacity to induce neutralizing antibodies against the vaccine strain is widely used as a surrogate for protection. However, the sensitivity of genetically distinct South American strains to vaccine-induced antibodies is unknown. Here, we show that antiviral potency of the polyclonal antibody response in both U.S. and Brazilian vaccinees is attenuated against an emergent Brazilian strain. This reduction was attributable to genetic changes at two sites in the central domain II of the glycoprotein E, including the acquisition of an N-linked glycosylation site, which are unique to and shared among most South American YFV strains. Our findings call for a reevaluation of current approaches to YFV immunological surveillance in South America and suggest approaches for designing updated vaccines.

microbiology↗

bioRxiv2019

A Zika Virus Primary Isolate Induces Neuroinflammation, Compromises the Blood-Brain Barrier, and Upregulates CXCL12 in Adult Macaques

Zika virus (ZIKV) is a neurotropic virus that can cause neuropathy in adults and fetal neurologic malformation following infection of pregnant women. We used a nonhuman primate model, the Indian-origin Rhesus macaque (IRM), to gain insight into virus-associated hallmarks of ZIKV-induced adult neuropathy. We find that the virus causes prevalent acute and chronic neuroinflammation and chronic disruption of the blood-brain barrier (BBB) in adult animals. Infection results in significant, targeted, and sustained upregulation of the chemokine, CXCL12, in the central nervous system (CNS). CXCL12 plays a key role both in regulating lymphocyte trafficking through the BBB to the CNS, and in mediating repair of damaged neural tissue including remyelination. Understanding how CXCL12 expression is controlled will likely be of central importance in the definition of ZIKV-associated neuropathy in adults. Author summaryZika virus (ZIKV) is a virus that can cause neurological problems in adults and damage to the fetal brain. Nonhuman primates (NHPs) are usually superior animal models for recapitulating human neurological disease because their brain, nervous system structure and immune response to virus infection are very similar to that of humans. We have studied the effect of ZIKV infection on the adult NHP brain and made several significant observations. Infection resulted in a high incidence of mild to moderate brain inflammation that persisted for a surprisingly long period of time. We also found that the virus disrupted the blood brain barrier, which is important for controlling transport of material from blood to the brain. It appears that the central nervous system expresses a specific substance in response to virus infection called a chemokine. This specific chemokine may be involved in virus-induced inflammation and/or in repair of virus-induced brain damage. Our data are significant since they help in understanding the mechanism of brain damage caused by ZIKV in adults.

microbiology↗

bioRxiv2019

Distinct YFV lineages co-circulated in the Central-Western and Southeastern Brazilian regions from 2015 to 2018

The current outbreak of yellow fever virus (YFV) that is afflicting Brazil since the end of 2016 probably originated from a re-introduction of YFV from endemic areas into the non-endemic Southeastern Brazil. However, the lack of genomic sequences from endemic regions hinders the tracking of YFVs dissemination routes. We assessed the origin and spread of the ongoing YFV Brazilian outbreak analyzing a new set of YFV strains infecting humans, non-human primates (NHP) and mosquitoes sampled across five Brazilian states from endemic and non-endemic regions between 2015 and 2018. We found two YFV sub-clade 1E lineages circulating in NHP from Goias state (GO), resulting from independent viral introductions into the Araguaia tributary river basin: while the strain from 2017 clustered intermingled with Venezuelan YFV strains from 2000, the YFV strain sampled in 2015 clustered with sequences of the current YFV outbreak in the Brazilian Southeastern region (named YFV2015-2018 lineage), displaying the same molecular signature associated to the current YFV outbreak. After its introduction in GO at around mid-2014, the YFV2015-2018 lineage followed two paths of dissemination outside GO, originating two major YFV sub-lineages: 1) the YFVMG/ES/RJ sub-lineage spread sequentially from the eastern area of Minas Gerais state to Espirito Santo and then to Rio de Janeiro states, following the Southeast Atlantic basin; 2) the YFVMG/SP sub-lineage spread from the southwestern area of Minas Gerais to the metropolitan region of Sao Paulo state, following the Parana basin. These results indicate the ongoing YFV outbreak in Southeastern Brazil originated from a dissemination event from GO almost two years before its recognition at the end of 2016. From GO this lineage was introduced in Minas Gerais state at least two times, originating two sub-lineages that followed different routes towards densely populated areas. The spread of YFV outside endemic regions for at least four years stresses the imperative importance of the continuous monitoring of YFV to aid decision-making for effective control policies aiming the increase of vaccination coverage to avoid the YFV transmission in densely populated urban centers.

epidemiology↗

bioRxiv2017

Genomic and structural features of the Yellow Fever virus from the 2016-2017 Brazilian outbreak

Brazil has been suffering a severe sylvatic epidemic of yellow fever virus (YFV) since late 2016. Analysis of full-length YFV genomes from all hosts involved in the Brazilian 2017 outbreak reveals that they belong to sub-lineage 1E within modern-lineage, but display several unique amino acid substitutions in highly conserved positions at NS3 and NS5 viral proteins. Evolutionary analyses indicate that YFV carrying that set of amino acid substitution circulates in the Southern Brazilian region for several months before being detected in December 2016. Structural and selection analyses support that some of these substitutions were under positive selection and could impact enzyme structure and function. Altogether, this evidence demonstrated that the current Brazilian YFV carries unique amino acid signatures in the non-structural proteins and support the hypothesis that those substitutions may be affecting the viral fitness and transmissibility.

microbiology↗