scholarly journals Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 902 ◽  
Author(s):  
Sodsai Tovanabutra ◽  
Rujipas Sirijatuphat ◽  
Phuc Pham ◽  
Lydia Bonar ◽  
Elizabeth Harbolick ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Envelope Gene ◽  
Founder Virus ◽  
Single Genome ◽  
The Central Nervous System ◽  
Acute Hiv ◽  
Tissue Compartments ◽  
Hiv 1

HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder (T/F) viruses differ between CNS and blood during AHI using single-genome sequencing of envelope gene and further examined subregions in pol and env using next-generation sequencing in paired plasma and cerebrospinal fluid (CSF) from 18 individuals. Different proportions of mostly minor variants were found in six of the eight multiple T/F-infected individuals, indicating enrichment of some variants in CSF that may lead to significant compartmentalization in the later stages of infection. This study provides evidence for the first time that HIV-1 compartmentalization in the CNS can occur within days of HIV-1 exposure in multiple T/F infections. Further understanding of factors that determine enrichment of T/F variants in the CNS, as well as potential long-term implications of these findings for persistence of HIV-1 reservoirs and neurological impairment in HIV, is needed.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

scholarly journals HIV-1 tropism for the central nervous system: Brain-derived envelope glycoproteins with lower CD4 dependence and reduced sensitivity to a fusion inhibitor

Virology ◽  
2006 ◽  
Vol 346 (1) ◽  
pp. 169-179 ◽  
Author(s):  
Julio Martín-García ◽  
Wei Cao ◽  
Angel Varela-Rohena ◽  
Matthew L. Plassmeyer ◽  
Francisco González-Scarano
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Envelope Glycoproteins ◽  
Fusion Inhibitor ◽  
The Central Nervous System ◽  
Hiv 1

scholarly journals R5 Macrophage-Tropic HIV-1 in the Male Genital Tract

2015 ◽  
Vol 89 (20) ◽  
pp. 10688-10692 ◽  
Author(s):  
Maria M. Bednar ◽  
Blake M. Hauser ◽  
Li-Hua Ping ◽  
Elena Dukhovlinova ◽  
Shuntai Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
Genital Tract ◽  
Male Genital Tract ◽  
The Central Nervous System ◽  
Hiv 1 ◽  
Male Genital

The entry tropism of HIV-1 Env proteins from virus isolated from the blood and genital tract of five men with compartmentalized lineages was determined. The Env proteins isolated from the genital tract of subject C018 were macrophage-tropic proteins, while the remaining clonedenvgenes encoded R5 T cell-tropic proteins. The detection of a macrophage-tropic lineage of HIV-1 within the male genital tract strongly suggests that evolution of macrophage-tropic viruses can occur in anatomically isolated sites outside the central nervous system.

scholarly journals Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection

2015 ◽  
Vol 11 (3) ◽  
pp. e1004720 ◽  
Author(s):  
Christa Buckheit Sturdevant ◽  
Sarah B. Joseph ◽  
Gretja Schnell ◽  
Richard W. Price ◽  
Ronald Swanstrom ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
The Central Nervous System ◽  
Hiv 1

scholarly journals Compartmentalization of HIV-1 in the central nervous system: role of the choroid plexus

AIDS ◽  
2005 ◽  
Vol 19 (7) ◽  
pp. 675-684 ◽  
Author(s):  
Evan J Burkala ◽  
Jun He ◽  
John T West ◽  
Charles Wood ◽  
Carol K Petito
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Choroid Plexus ◽  
The Central Nervous System ◽  
Hiv 1

scholarly journals Enhanced Mucosal Immunoglobulin A Response of Intranasal Adenoviral Vector Human Immunodeficiency Virus Vaccine and Localization in the Central Nervous System

2003 ◽  
Vol 77 (18) ◽  
pp. 10078-10087 ◽  
Author(s):  
Franck Lemiale ◽  
Wing-pui Kong ◽  
Levent M. Akyürek ◽  
Xu Ling ◽  
Yue Huang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Human Immunodeficiency Virus ◽  
Nervous System ◽  
Viral Vector ◽  
Recombinant Adenovirus ◽  
Immunoglobulin A ◽  
Retrograde Transport ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
Hiv 1

ABSTRACT Replication-defective adenovirus (ADV) vectors represent a promising potential platform for the development of a vaccine for AIDS. Although this vector is typically administered intramuscularly, it would be desirable to induce mucosal immunity by delivery through alternative routes. In this study, the immune response and biodistribution of ADV vectors delivered by different routes were evaluated. ADV vectors expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pol, and Env were delivered intramuscularly or intranasally into mice. Intranasal immunization induced greater HIV-specific immunoglobulin A (IgA) responses in mucosal secretions and sera than in animals with intramuscular injection, which showed stronger systemic cellular and IgG responses. Administration of the vaccine through an intranasal route failed to overcome prior ADV immunity. Animals exposed to ADV prior to vaccination displayed substantially reduced cellular and humoral immune responses to HIV antigens in both groups, though the reduction was greater in animals immunized intranasally. This inhibition was partially overcome by priming with a DNA expression vector expressing HIV-1 Gag, Pol, and Env before boosting with the viral vector. Biodistribution of recombinant adenovirus (rADV) vectors administered intranasally revealed infection of the central nervous system, specifically in the olfactory bulb, possibly via retrograde transport by olfactory neurons in the nasal epithelium, which may limit the utility of this route of delivery of ADV vector-based vaccines.

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