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Targeting HIV-1 innate immune responses therapeutically
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology.
Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
2011 (English)In: Current Opinion in HIV & AIDS, ISSN 1746-630X, Vol. 6, no 5, 435-443 p.Article in journal (Refereed) Published
Abstract [en]

Purpose of review less thanbrgreater than less thanbrgreater thanThe early stage of HIV-1 infection is when the virus is most vulnerable, and should therefore offer the best opportunity for therapeutic interventions. This review addresses the recent progress in the understanding of innate immune responses against HIV-1 with focus on the potential targets for prevention of viral acquisition, replication and dissemination. less thanbrgreater than less thanbrgreater thanRecent findings less thanbrgreater than less thanbrgreater thanResearch indicates that the host-derived factor trappin-2/elafin is protective against HIV, whereas semen-derived enhancer of viral infection and defensins 5 and 6 enhance viral transmission. Further, studies suggest that stimulation of TLR4 and inhibition of TLR7-9 pathways may be HIV suppressive. The regulation and function of viral restriction factors tetherin and APOBEC3G have been investigated and a molecule mimicking the premature uncoating achieved by TRIM5 alpha, PF74, has been identified. Chloroquine has been shown to inhibit plasmacytoid dendritic cell activation and suppress negative modulators of T-cell responses. Blockade of HMBG1 has been found to restore natural-killer-cell-mediated killing of infected dendritic cells, normally suppressed by HIV-1. Interestingly, when used as adjuvants, EAT-2 and heat shock protein gp96 reportedly enhance innate immune responses. less thanbrgreater than less thanbrgreater thanSummary less thanbrgreater than less thanbrgreater thanSeveral targets for innate immunity-mediated therapeutics have been identified. Nonetheless, more research is required to unveil their underlying mechanisms and interactions before testing these molecules in clinical trials.

Place, publisher, year, edition, pages
Lippincott, Williams and Wilkins , 2011. Vol. 6, no 5, 435-443 p.
Keyword [en]
HIV, innate, microbicides, therapeutics
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-71554DOI: 10.1097/COH.0b013e32834970d8ISI: 000295515400014OAI: oai:DiVA.org:liu-71554DiVA: diva2:450523
Note
Funding Agencies|Swedish Research Council|AI52731 |Swedish Physicians against AIDS Research Foundation||Swedish International Development Cooperation Agency||SIDA SARC||VINNMER for Vinnova||Linkoping University Hospital||CALF||Swedish Society of Medicine||Available from: 2011-10-21 Created: 2011-10-21 Last updated: 2012-03-25

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Ellegård, RadaShankar, EsakimuthuLarsson, Marie

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