scholarly journals Membrane Interference Against HIV-1 by Intrinsic Antiviral Factors: The Case of IFITMs

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1171
Author(s):  
Federico Marziali ◽  
Andrea Cimarelli
Keyword(s):  
Restriction Factors ◽  
Defense Proteins ◽  
Innate Defense ◽  
Cellular Processes ◽  
Crucial Component ◽  
The Family ◽  
To Come ◽  
Definition Of ◽  
Hiv 1 ◽  
Replicative Cycle

HIV-1 is a complex retrovirus that is adapted to replicate in cells of the immune system. To do so, HIV-1, like other viruses, developed strategies to use several cellular processes to its advantage, but had also to come to terms with an arsenal of cellular innate defense proteins, or antiviral factors, that target more or less efficiently, virtually every step of the virus replicative cycle. Among antiviral restriction factors, the family of interferon-induced transmembrane proteins (IFITMs) has emerged as a crucial component of cellular innate defenses for their ability to interfere with both early and late phases of viral replication by inhibiting cellular and viral membranes fusion. Here, we review the enormous advances made since the discovery of IFITMs as interferon-regulated genes more than thirty years ago, with a particular focus on HIV-1 and on the elements that modulate its susceptibility or resistance towards members of this family. Given the recent advances of the field in the elucidation of the mechanism of IFITM inhibition and on the mechanism(s) of viral resistance, we expect that future years will bring novel insights into the definition of the multiple facets of IFITMs and on their possible use for novel therapeutical approaches.

scholarly journals From Entry to Egress: Strategic Exploitation of the Cellular Processes by HIV-1

2020 ◽  
Vol 11 ◽  
Author(s):  
Pavitra Ramdas ◽  
Amit Kumar Sahu ◽  
Tarun Mishra ◽  
Vipin Bhardwaj ◽  
Ajit Chande
Keyword(s):  
Life Cycle ◽  
Nuclear Import ◽  
Arms Race ◽  
Surface Proteins ◽  
Restriction Factors ◽  
Host Restriction ◽  
Cellular Processes ◽  
Host Restriction Factors ◽  
Post Entry ◽  
Hiv 1

HIV-1 employs a rich arsenal of viral factors throughout its life cycle and co-opts intracellular trafficking pathways. This exquisitely coordinated process requires precise manipulation of the host microenvironment, most often within defined subcellular compartments. The virus capitalizes on the host by modulating cell-surface proteins and cleverly exploiting nuclear import pathways for post entry events, among other key processes. Successful virus–cell interactions are indeed crucial in determining the extent of infection. By evolving defenses against host restriction factors, while simultaneously exploiting host dependency factors, the life cycle of HIV-1 presents a fascinating montage of an ongoing host–virus arms race. Herein, we provide an overview of how HIV-1 exploits native functions of the host cell and discuss recent findings that fundamentally change our understanding of the post-entry replication events.

scholarly journals APOBEC3 versus Retroviruses, Immunity versus Invasion: Clash of the Titans

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Ann M. Sheehy ◽  
Julie Erthal
Keyword(s):  
Clinical Intervention ◽  
Immune Defense ◽  
Restriction Factors ◽  
Defense Proteins ◽  
Tremendous Amount ◽  
Unexpected Findings ◽  
And Function ◽  
Vif Protein ◽  
Hiv 1

Since the identification of APOBEC3G (A3G) as a potent restriction factor of HIV-1, a tremendous amount of effort has led to a broadened understanding of both A3G and the APOBEC3 (A3) family to which it belongs. In spite of the fine-tuned viral counterattack to A3 activity, in the form of the HIV-1 Vif protein, enthusiasm for leveraging the Vif : A3G axis as a point of clinical intervention remains high. In an impressive explosion of information over the last decade, additional A3 family members have been identified as antiviral proteins, mechanistic details of the restrictive capacity of these proteins have been elucidated, structure-function studies have revealed important molecular details of the Vif : A3G interaction, and clinical cohorts have been scrutinized for correlations between A3 expression and function and viral pathogenesis. In the last year, novel and unexpected findings regarding the role of A3G in immunity have refocused efforts on exploring the potential of harnessing the natural power of this immune defense. These most recent reports allude to functions of the A3 proteins that extend beyond their well-characterized designation as restriction factors. The emerging story implicates the A3 family as not only defense proteins, but also as participants in the broader innate immune response.

scholarly journals A general model for retroviral capsid pattern recognition by TRIM5 proteins

2017 ◽  
pp. JVI.01563-17 ◽  
Author(s):  
Jonathan M. Wagner ◽  
Devin E. Christensen ◽  
Akash Bhattacharya ◽  
Daria M. Dawidziak ◽  
Marcin D. Roganowicz ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Sequence Similarity ◽  
Hexagonal Lattice ◽  
Cyclophilin A ◽  
Higher Order ◽  
Restriction Factors ◽  
Defense Proteins ◽  
Spry Domain ◽  
Capsid Shell ◽  
Hiv 1

Restriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5 proteins, which recognize the viral capsid shell that surrounds, organizes, and protects the viral genome. TRIM5α uses a SPRY domain to bind capsids with low intrinsic affinity (KD>1 mM), and therefore requires higher-order assembly into a hexagonal lattice to generate sufficient avidity for productive capsid recognition. TRIMCyp, on the other hand, binds HIV-1 capsids through a cyclophilin A domain, which has a well-defined binding site and higher (KD∼10 μM) affinity for isolated capsid subunits. It has therefore been argued that TRIMCyp proteins may have dispensed with the need for higher-order assembly to function as antiviral factors. Here, we show that, consistent with its high degree of sequence similarity with TRIM5α, the TRIMCyp B-box 2 domain shares the same ability to self-associate and facilitate assembly of a TRIMCyp hexagonal lattice that can wrap about the HIV-1 capsid. We also show that under stringent experimental conditions, TRIMCyp-mediated restriction of HIV-1 is indeed dependent on higher-order assembly. Both forms of TRIM5 therefore use the same mechanism of avidity-driven capsid pattern recognition.IMPORTANCERhesus macaques and owl monkeys are highly resistant to HIV-1 infection due to the activity of TRIM5 restriction factors. The rhesus macaque TRIM5α protein blocks HIV-1 through a mechanism that requires self-assembly of a hexagonal TRIM5α lattice around the invading viral core. Lattice assembly amplifies very weak interactions between the TRIM5α SPRY domain and the HIV-1 capsid. Assembly also promotes dimerization of the TRIM5α RING E3 ligase domain, resulting in synthesis of polyubiquitin chains that mediate downstream steps of restriction. In contrast to rhesus TRIM5α, the owl monkey TRIM5 homolog, TRIMCyp, binds isolated HIV-1 CA subunits more tightly through its cyclophilin A domain, and was therefore thought to act independent of higher-order assembly. Here, we show that TRIMCyp shares the assembly properties of TRIM5α and that both forms of TRIM5 use the same mechanism of hexagonal lattice formation to promote viral recognition and restriction.

scholarly journals APOBEC3H Subcellular Localization Determinants Define Zipcode for Targeting HIV-1 for Restriction

2018 ◽  
Vol 38 (23) ◽  
Author(s):  
Daniel J. Salamango ◽  
Jordan T. Becker ◽  
Jennifer L. McCann ◽  
Adam Z. Cheng ◽  
Özlem Demir ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Nuclear Import ◽  
Cell Types ◽  
Restriction Factors ◽  
Structural Determinants ◽  
Cellular Processes ◽  
Biological Studies ◽  
Multiple Cell ◽  
Import And Export ◽  
Hiv 1

ABSTRACT APOBEC enzymes are DNA cytosine deaminases that normally serve as virus restriction factors, but several members, including APOBEC3H, also contribute to cancer mutagenesis. Despite their importance in multiple fields, little is known about cellular processes that regulate these DNA mutating enzymes. We show that APOBEC3H exists in two distinct subcellular compartments, cytoplasm and nucleolus, and that the structural determinants for each mechanism are genetically separable. First, native and fluorescently tagged APOBEC3Hs localize to these two compartments in multiple cell types. Second, a series of genetic, pharmacologic, and cell biological studies demonstrate active cytoplasmic and nucleolar retention mechanisms, whereas nuclear import and export occur through passive diffusion. Third, APOBEC3H cytoplasmic retention determinants relocalize APOBEC3A from a passive cell-wide state to the cytosol and, additionally, endow potent HIV-1 restriction activity. These results indicate that APOBEC3H has a structural zipcode for subcellular localization and selecting viral substrates for restriction.

REGULATION OF MARRIAGE RELATIONS IN THE TURKESTAN REGION

2019 ◽  
Vol 22 (2) ◽  
pp. 27-32
Author(s):  
Khurshida Tillahodjaeva ◽  
Keyword(s):  
The Family ◽  
Role Of Women ◽  
Family And Marriage ◽  
Material Conditions ◽  
Definition Of

In this article we will talk about the scale of family and marriage relations in the early XX century in the Turkestan region, their regulation, legislation. Clearly reveals the role of women and men in the family, the definition of which is based on the material conditions of society, equality of rights and freedoms and its features.

Restriction Factors in HIV-1 Disease Progression

2015 ◽  
Vol 13 (6) ◽  
pp. 448-461 ◽  
Author(s):  
Natacha Merindol ◽  
Lionel Berthoux
Keyword(s):  
Disease Progression ◽  
Restriction Factors ◽  
Hiv 1

Human Fallibility and Fallibilism about Knowledge

2018 ◽  
Author(s):  
Jessica Brown
Keyword(s):  
Practical Reasoning ◽  
Knowledge Attributions ◽  
Knowledge Norm ◽  
Concessive Knowledge Attributions ◽  
To Come ◽  
Definition Of ◽  
Threshold Problem

This chapter distinguishes between fallibilism and infallibilism by appeal to entailment: infallibilists hold that knowledge that p requires evidence which entails that p; fallibilists deny that. It outlines some of the recent motivations for infallibilism, including the infelicity of concessive knowledge attributions, the threshold problem, closure, and the knowledge norm of practical reasoning. Further, we see how contemporary infallibilists attempt to avoid scepticism by appeal either to a generous conception of evidence or a shifty view of knowledge, such as contextualism. The chapter explains the book’s focus on non-shifty versions of infallibilism which defend a generous conception of evidence. It ends by defending the entailment definition of infallibilism over other potential definitions, and outlining the chapters to come.

scholarly journals Foamy Viruses, Bet, and APOBEC3 Restriction

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 504
Author(s):  
Ananda Ayyappan Jaguva Vasudevan ◽  
Daniel Becker ◽  
Tom Luedde ◽  
Holger Gohlke ◽  
Carsten Münk
Keyword(s):  
Current Knowledge ◽  
Regulatory Protein ◽  
Host Population ◽  
Life Cycles ◽  
Restriction Factors ◽  
Host Restriction ◽  
Open Questions ◽  
Foamy Viruses ◽  
Natural Hosts ◽  
Hiv 1

Non-human primates (NHP) are an important source of viruses that can spillover to humans and, after adaptation, spread through the host population. Whereas HIV-1 and HTLV-1 emerged as retroviral pathogens in humans, a unique class of retroviruses called foamy viruses (FV) with zoonotic potential are occasionally detected in bushmeat hunters or zookeepers. Various FVs are endemic in numerous mammalian natural hosts, such as primates, felines, bovines, and equines, and other animals, but not in humans. They are apathogenic, and significant differences exist between the viral life cycles of FV and other retroviruses. Importantly, FVs replicate in the presence of many well-defined retroviral restriction factors such as TRIM5α, BST2 (Tetherin), MX2, and APOBEC3 (A3). While the interaction of A3s with HIV-1 is well studied, the escape mechanisms of FVs from restriction by A3 is much less explored. Here we review the current knowledge of FV biology, host restriction factors, and FV–host interactions with an emphasis on the consequences of FV regulatory protein Bet binding to A3s and outline crucial open questions for future studies.

scholarly journals Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters

2021 ◽  
Vol 22 (9) ◽  
pp. 4716
Author(s):  
Francesco Ciscato ◽  
Lavinia Ferrone ◽  
Ionica Masgras ◽  
Claudio Laquatra ◽  
Andrea Rasola
Keyword(s):  
Endoplasmic Reticulum ◽  
Aerobic Glycolysis ◽  
Neoplastic Progression ◽  
Malignant Growth ◽  
Hexokinase 2 ◽  
Genetic Ablation ◽  
Contact Points ◽  
Survival Pathways ◽  
The Family ◽  
Definition Of

Hexokinases are a family of ubiquitous exose-phosphorylating enzymes that prime glucose for intracellular utilization. Hexokinase 2 (HK2) is the most active isozyme of the family, mainly expressed in insulin-sensitive tissues. HK2 induction in most neoplastic cells contributes to their metabolic rewiring towards aerobic glycolysis, and its genetic ablation inhibits malignant growth in mouse models. HK2 can dock to mitochondria, where it performs additional functions in autophagy regulation and cell death inhibition that are independent of its enzymatic activity. The recent definition of HK2 localization to contact points between mitochondria and endoplasmic reticulum called Mitochondria Associated Membranes (MAMs) has unveiled a novel HK2 role in regulating intracellular Ca2+ fluxes. Here, we propose that HK2 localization in MAMs of tumor cells is key in sustaining neoplastic progression, as it acts as an intersection node between metabolic and survival pathways. Disrupting these functions by targeting HK2 subcellular localization can constitute a promising anti-tumor strategy.

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