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The nerve growth factor reduces APOBEC3G synthesis and enhances HIV-1 transcription and replication in human primary macrophages.
MedLine Citation:
PMID:  21217078     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Macrophages infected with HIV-1 sustain viral replication for long periods, functioning as viral reservoirs. Therefore, recognition of factors that maintain macrophages alive and influence HIV-1 replication is critical to understanding the mechanisms that regulate HIV-1 replicative cycle. Because HIV-1-infected macrophages release the nerve growth factor (NGF), and NGF neutralization reduces viral production, we further analyzed how this molecule affects HIV-1 replication. Here, we show that NGF stimulates HIV-1 replication in primary macrophages by means of signaling through its high affinity receptor TrKA, and with the involvement of reticular calcium, PKC, ERK, p38 kinase, and NF-kB. NGF-induced enhancement of HIV-1 replication occurred during the late events of HIV-1 replicative cycle, with a concomitant increase in viral transcription and production. In addition, NGF reduced the synthesis of the cellular HIV-1 restriction factor APOBEC3G (A3G), as well as overrode the IFN-γ-induced up-regulation of A3G, allowing the production of a well-fitted virus. Since NGF-TrKA signaling is a crucial event for macrophage survival, it is possible that the NGF-induced HIV-1 replication plays a role for the maintenance of HIV-1 reservoirs. Our study could contribute to the understanding of immunopathogenesis of HIV-1 infection and might provide insights about approaches aimed to limit viral replication in HIV-1 reservoirs.
Authors:
Thiago Moreno L Souza; Diego Q Rodrigues; Caroline P B Passaes; Victor Barreto-de-Souza; Renato S Aguiar; Jairo R Temerozo; Mariza G Morgado; Carlos Frederico L Fontes; Elizabeth G Araujo; Dumith Chequer Bou-Habib
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-7
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, Brazil;
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