70 research outputs found
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A Role for Nuclear F-Actin Induction in Human Cytomegalovirus Nuclear Egress
ABSTRACT Herpesviruses, which include important pathogens, remodel the host cell nucleus to facilitate infection. This remodeling includes the formation of structures called replication compartments (RCs) in which herpesviruses replicate their DNA. During infection with the betaherpesvirus, human cytomegalovirus (HCMV), viral DNA synthesis occurs at the periphery of RCs within the nuclear interior, after which assembled capsids must reach the inner nuclear membrane (INM) for translocation to the cytoplasm (nuclear egress). The processes that facilitate movement of HCMV capsids to the INM during nuclear egress are unknown. Although an actin-based mechanism of alphaherpesvirus capsid trafficking to the INM has been proposed, it is controversial. Here, using a fluorescently-tagged, nucleus-localized actin-binding peptide, we show that HCMV, but not herpes simplex virus 1, strongly induced nuclear actin filaments (F-actin) in human fibroblasts. Based on studies using UV inactivation and inhibitors, this induction depended on viral gene expression. Interestingly, by 24 h postinfection, nuclear F-actin formed thicker structures that appeared by super-resolution microscopy to be bundles of filaments. Later in infection, nuclear F-actin primarily localized along the RC periphery and between the RC periphery and the nuclear rim. Importantly, a drug that depolymerized nuclear F-actin caused defects in production of infectious virus, capsid accumulation in the cytoplasm, and capsid localization near the nuclear rim, without decreasing capsid accumulation in the nucleus. Thus, our results suggest that for at least one herpesvirus, nuclear F-actin promotes capsid movement to the nuclear periphery and nuclear egress. We discuss our results in terms of competing models for these processes
Full genome sequence and sfRNA interferon antagonist activity of Zika virus from Recife, Brazil
Background:
The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into a major public health concern. Little is currently known about the evolution and biology of ZIKV and the factors that contribute to the associated pathogenesis. Determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative processes and virus-host interactions.
Methodology/Principal findings:
We obtained a ZIKV isolate from a patient who presented with classical ZIKV-associated symptoms, and used high throughput sequencing and other molecular biology approaches to determine its full genome sequence, including non-coding regions. Genome regions were characterized and compared to the sequences of other isolates where available. Furthermore, we identified a subgenomic flavivirus RNA (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced type I interferon induction, with a lesser effect on MDA-5 mediated action.
Conclusions/Significance:
The full-length genome sequence including non-coding regions of a South American ZIKV isolate from a patient with classical symptoms will support efforts to develop genetic tools for this virus. Detection of sfRNA that counteracts interferon responses is likely to be important for further understanding of pathogenesis and virus-host interactions
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COVID-19, systemic crisis, and possible implications for the wild meat trade in sub-Saharan Africa
Wild animals play an integral and complex role in the economies and ecologies of many
countries across the globe, including those of West and Central Africa, the focus of this
policy perspective. The trade in wild meat, and its role in diets, have been brought into
focus as a consequence of discussions over the origins of COVID-19. As a result, there
have been calls for the closure of China’s “wet markets”; greater scrutiny of the wildlife
trade in general; and a spotlight has been placed on the potential risks posed by growing human populations and shrinking natural habitats for animal to human transmission of
zoonotic diseases. However, to date there has been little attention given to what the consequences of the COVID-19 economic shock may be for the wildlife trade; the people who
rely on it for their livelihoods; and the wildlife that is exploited. In this policy perspective,
we argue that the links between the COVID-19 pandemic, rural livelihoods and wildlife
are likely to be more complex, more nuanced, and more far-reaching, than is represented in
the literature to date. We develop a causal model that tracks the likely implications for the
wild meat trade of the systemic crisis triggered by COVID-19. We focus on the resulting
economic shockwave, as manifested in the collapse in global demand for commodities such
as oil, and international tourism services, and what this may mean for local African economies and livelihoods. We trace the shockwave through to the consequences for the use
of, and demand for, wild meats as households respond to these changes. We suggest that
understanding and predicting the complex dynamics of wild meat use requires increased
collaboration between environmental and resource economics and the ecological and conservation sciences
A difusão da doutrina da circulação do sangue: a correspondência entre William Harvey e Caspar Hofmann em maio de 1636
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant
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