Retroviral Infections of the Nervous System

2021 ◽  
pp. 1009-1015
Author(s):  
Michel Toledano ◽  
Allen J. Aksamit Jr
Keyword(s):  
Nervous System ◽  
Reverse Transcription ◽  
Rna Viruses ◽  
Neurologic Manifestations ◽  
T Lymphotropic Virus ◽  
System P ◽  
Aids Pandemic ◽  
The Family ◽  
Retroviral Infections ◽  
Hiv 1

Retroviruses are a family of RNA viruses that replicate by reverse transcription. The family includes HIV and human T-lymphotropic virus. This chapter reviews neurologic manifestations of these retroviruses. A retrovirus in the genus Lentivirus, HIV has 2 forms, HIV-1 and HIV-2. HIV-1 is associated with the global AIDS pandemic, whereas HIV-2 causes an AIDS-like illness primarily in West Africa, although pockets of infection exist globally.

scholarly journals Primate TRIM5 proteins form hexagonal nets on HIV-1 capsids

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Yen-Li Li ◽  
Viswanathan Chandrasekaran ◽  
Stephen D Carter ◽  
Cora L Woodward ◽  
Devin E Christensen ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Reverse Transcription ◽  
Cyclophilin A ◽  
Restriction Factors ◽  
Viral Capsids ◽  
Ring Domains ◽  
Conformational Plasticity ◽  
Retroviral Infections ◽  
Hiv 1 ◽  
Terminal Domains

TRIM5 proteins are restriction factors that block retroviral infections by binding viral capsids and preventing reverse transcription. Capsid recognition is mediated by C-terminal domains on TRIM5α (SPRY) or TRIMCyp (cyclophilin A), which interact weakly with capsids. Efficient capsid recognition also requires the conserved N-terminal tripartite motifs (TRIM), which mediate oligomerization and create avidity effects. To characterize how TRIM5 proteins recognize viral capsids, we developed methods for isolating native recombinant TRIM5 proteins and purifying stable HIV-1 capsids. Biochemical and EM analyses revealed that TRIM5 proteins assembled into hexagonal nets, both alone and on capsid surfaces. These nets comprised open hexameric rings, with the SPRY domains centered on the edges and the B-box and RING domains at the vertices. Thus, the principles of hexagonal TRIM5 assembly and capsid pattern recognition are conserved across primates, allowing TRIM5 assemblies to maintain the conformational plasticity necessary to recognize divergent and pleomorphic retroviral capsids.

scholarly journals Varicella (Human Herpes Virus-3) Vaccine Potential Role Against Herpes (HSV-1/HSV-2) Viruses to Prevent HIV-1 Pandemic in Sub- Saharan Africa

2018 ◽  
Vol 10 (1) ◽  
pp. 116-123
Author(s):  
Jacqueline Le Goaster ◽  
Patrice Bourée ◽  
Franck N. El Sissy ◽  
Johanna Pokossy Epee ◽  
Frédéric Tangy ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Rna Viruses ◽  
Varicella Vaccine ◽  
Sub Saharan Africa ◽  
Dna And Rna ◽  
Aids Pandemic ◽  
Recurrent Herpes ◽  
Sub Saharan ◽  
Hiv 1 ◽  
Hsv 1

Background: Synergy exists between DNA and RNA viruses. It was found that the Human Immunodeficiency Viruses (HIV-1) are RNA viruses at the origin of Acquired Immune Deficiency Syndrome (AIDS). The DNA recurrent herpes diseases are associated to AIDS virus at the origin of Sub-Saharan cancer AIDS pandemic. Objective: It is speculated that a varicella virus (HHV-3) immune defect could originate HSV- 1/HSV-2 recurrent herpes diseases that can be cured by varicella vaccine (2012). Methods: At a Symposium held in Kampala, Uganda (1962), impressive Sub-Saharan cancer epidemics: Hodgkin lymphomas and Kaposi sarcomas have been reported since the onset of the 20th century and remained unexplained. Over one thousand publications related to these cancer epidemics were presented. For millenniums, Bantu populations have been living in tropical forests close to chimpanzees infected by Simian Immune Deficiency viruses (SIV). SIV became Human Immune Deficiency viruses (HIV-1). AIDS is a zoonosis. Results: The DNA and RNA viruses, herpes with HIV-1 viruses, are correlated to Sub- Saharan AIDS infections. They induce an extensive immune deficiency with other herpes viruses such as HHV-4 and HHV-8, which are linked to lymphomas and Kaposi sarcomas. It is postulated that a primary HHV-3 immune weakness could be linked to herpes partnership with AIDS pandemic. Conclusion: The Oka, anti-HHV-3, varicella vaccine is able to cure HSV1/HSV2 recurrent herpes diseases. It induces a specific increase of the varicella antibodies. Thus varicella vaccination could prevent herpes recurrences in Sub-Saharan Africa. One- child dose varicella vaccine could be proposed as the first step to overcome HHV-3 herpes deficiency in order to prevent AIDS pandemic.

Developmental abnormalities of the central nervous system

2020 ◽  
pp. 6350-6367
Author(s):  
Christopher M. Verity ◽  
Jane A. Hurst ◽  
Helen V. Firth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Complex Structure ◽  
Nervous System Development ◽  
Developmental Abnormalities ◽  
System P ◽  
The Family ◽  
The Central Nervous System ◽  
Brain And Spinal Cord

This chapter deals with abnormalities that may result from failures at particular stages of central nervous system development. The brain and spinal cord arise from a sheet of cells that undergo transformations into the final complex structure. Failure of closure of the neural tube may result in anencephaly or spina bifida and failure of regionalization may cause holoprosencephaly. Disorders of neural proliferation or migration cause abnormalities of the cerebral cortex. There are distinct malformations of the posterior fossa structures and there are complex malformations that cannot be ascribed to just one abnormal step in development. The clinical problems associated with developmental abnormalities of the central nervous system are discussed and the approach to obtaining a clinical molecular diagnosis and providing genetic advice to the family is outlined.

Glial Cells in the Auditory Brainstem

2018 ◽  
pp. 680-706
Author(s):  
Giedre Milinkeviciute ◽  
Karina S. Cramer
Keyword(s):  
Nervous System ◽  
Glial Cells ◽  
Sound Localization ◽  
Auditory Brainstem ◽  
Synaptic Function ◽  
System Function ◽  
Auditory Neurons ◽  
System P ◽  
The Central Nervous System ◽  
Nervous System Function

The auditory brainstem carries out sound localization functions that require an extraordinary degree of precision. While many of the specializations needed for these functions reside in auditory neurons, additional adaptations are made possible by the functions of glial cells. Astrocytes, once thought to have mainly a supporting role in nervous system function, are now known to participate in synaptic function. In the auditory brainstem, they contribute to development of specialized synapses and to mature synaptic function. Oligodendrocytes play critical roles in regulating timing in sound localization circuitry. Microglia enter the central nervous system early in development, and also have important functions in the auditory system’s response to injury. This chapter highlights the unique functions of these non-neuronal cells in the auditory system.

scholarly journals SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Charlotte Martinat ◽  
Arthur Cormier ◽  
Joëlle Tobaly-Tapiero ◽  
Noé Palmic ◽  
Nicoletta Casartelli ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Reverse Transcription ◽  
Immune Cells ◽  
Viral Restriction ◽  
Antiviral Function ◽  
Hiv 1 ◽  
Constitutively Active

AbstractSAMHD1 is a cellular triphosphohydrolase (dNTPase) proposed to inhibit HIV-1 reverse transcription in non-cycling immune cells by limiting the supply of the dNTP substrates. Yet, phosphorylation of T592 downregulates SAMHD1 antiviral activity, but not its dNTPase function, implying that additional mechanisms contribute to viral restriction. Here, we show that SAMHD1 is SUMOylated on residue K595, a modification that relies on the presence of a proximal SUMO-interacting motif (SIM). Loss of K595 SUMOylation suppresses the restriction activity of SAMHD1, even in the context of the constitutively active phospho-ablative T592A mutant but has no impact on dNTP depletion. Conversely, the artificial fusion of SUMO2 to a non-SUMOylatable inactive SAMHD1 variant restores its antiviral function, a phenotype that is reversed by the phosphomimetic T592E mutation. Collectively, our observations clearly establish that lack of T592 phosphorylation cannot fully account for the restriction activity of SAMHD1. We find that SUMOylation of K595 is required to stimulate a dNTPase-independent antiviral activity in non-cycling immune cells, an effect that is antagonized by cyclin/CDK-dependent phosphorylation of T592 in cycling cells.

scholarly journals High-resolution view of HIV-1 reverse transcriptase initiation complexes and inhibition by NNRTI drugs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Betty Ha ◽  
Kevin P. Larsen ◽  
Jingji Zhang ◽  
Ziao Fu ◽  
Elizabeth Montabana ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Viral Entry ◽  
Reverse Transcription ◽  
Molecular Mechanisms ◽  
Dissociation Kinetics ◽  
Structural Mechanism ◽  
Medium Resolution ◽  
Kinetics Of ◽  
Hiv 1

AbstractReverse transcription of the HIV-1 viral RNA genome (vRNA) is an integral step in virus replication. Upon viral entry, HIV-1 reverse transcriptase (RT) initiates from a host tRNALys3 primer bound to the vRNA genome and is the target of key antivirals, such as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Initiation proceeds slowly with discrete pausing events along the vRNA template. Despite prior medium-resolution structural characterization of reverse transcriptase initiation complexes (RTICs), higher-resolution structures of the RTIC are needed to understand the molecular mechanisms that underlie initiation. Here we report cryo-EM structures of the core RTIC, RTIC–nevirapine, and RTIC–efavirenz complexes at 2.8, 3.1, and 2.9 Å, respectively. In combination with biochemical studies, these data suggest a basis for rapid dissociation kinetics of RT from the vRNA–tRNALys3 initiation complex and reveal a specific structural mechanism of nucleic acid conformational stabilization during initiation. Finally, our results show that NNRTIs inhibit the RTIC and exacerbate discrete pausing during early reverse transcription.

scholarly journals Extended Interactions between HIV-1 Viral RNA and tRNALys3 Are Important to Maintain Viral RNA Integrity

2020 ◽  
Vol 22 (1) ◽  
pp. 58
Author(s):  
Thomas Gremminger ◽  
Zhenwei Song ◽  
Juan Ji ◽  
Avery Foster ◽  
Kexin Weng ◽  
...  
Keyword(s):  
Reverse Transcription ◽  
Potential Interaction ◽  
Viral Rna ◽  
Primer Binding Site ◽  
Rna Integrity ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Extended Interaction ◽  
Hiv 1

The reverse transcription of the human immunodeficiency virus 1 (HIV-1) initiates upon annealing of the 3′-18-nt of tRNALys3 onto the primer binding site (PBS) in viral RNA (vRNA). Additional intermolecular interactions between tRNALys3 and vRNA have been reported, but their functions remain unclear. Here, we show that abolishing one potential interaction, the A-rich loop: tRNALys3 anticodon interaction in the HIV-1 MAL strain, led to a decrease in viral infectivity and reduced the synthesis of reverse transcription products in newly infected cells. In vitro biophysical and functional experiments revealed that disruption of the extended interaction resulted in an increased affinity for reverse transcriptase (RT) and enhanced primer extension efficiency. In the absence of deoxyribose nucleoside triphosphates (dNTPs), vRNA was degraded by the RNaseH activity of RT, and the degradation rate was slower in the complex with the extended interaction. Consistently, the loss of vRNA integrity was detected in virions containing A-rich loop mutations. Similar results were observed in the HIV-1 NL4.3 strain, and we show that the nucleocapsid (NC) protein is necessary to promote the extended vRNA: tRNALys3 interactions in vitro. In summary, our data revealed that the additional intermolecular interaction between tRNALys3 and vRNA is likely a conserved mechanism among various HIV-1 strains and protects the vRNA from RNaseH degradation in mature virions.

scholarly journals An assessment of the reproducibility of reverse transcription digital PCR quantification of HIV-1

Methods ◽  
2021 ◽  
Author(s):  
Samreen Falak ◽  
Rainer Macdonald ◽  
Eloise J. Busby ◽  
Denise M.O'Sullivan ◽  
Mojca Milavec ◽  
...  
Keyword(s):  
Reverse Transcription ◽  
Digital Pcr ◽  
Hiv 1

scholarly journals From Capsids to Complexes: Expanding the Role of TRIM5α in the Restriction of Divergent RNA Viruses and Elements

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 446
Author(s):  
Kevin M. Rose ◽  
Stephanie J. Spada ◽  
Rebecca Broeckel ◽  
Kristin L. McNally ◽  
Vanessa M. Hirsch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Molecular Basis ◽  
Human Population ◽  
Rna Viruses ◽  
Arms Race ◽  
Innate Immune ◽  
Immunodeficiency Virus ◽  
Underlying Mechanisms ◽  
Hiv 1

An evolutionary arms race has been ongoing between retroviruses and their primate hosts for millions of years. Within the last century, a zoonotic transmission introduced the Human Immunodeficiency Virus (HIV-1), a retrovirus, to the human population that has claimed the lives of millions of individuals and is still infecting over a million people every year. To counteract retroviruses such as this, primates including humans have evolved an innate immune sensor for the retroviral capsid lattice known as TRIM5α. Although the molecular basis for its ability to restrict retroviruses is debated, it is currently accepted that TRIM5α forms higher-order assemblies around the incoming retroviral capsid that are not only disruptive for the virus lifecycle, but also trigger the activation of an antiviral state. More recently, it was discovered that TRIM5α restriction is broader than previously thought because it restricts not only the human retroelement LINE-1, but also the tick-borne flaviviruses, an emergent group of RNA viruses that have vastly different strategies for replication compared to retroviruses. This review focuses on the underlying mechanisms of TRIM5α-mediated restriction of retroelements and flaviviruses and how they differ from the more widely known ability of TRIM5α to restrict retroviruses.

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