HIV restriction by APOBEC3 in humanized mice.

Innate immune restriction factors represent important specialized barriers to zoonotic transmission of viruses. Significant consideration has been given to their possible use for therapeutic benefit. The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) family of cytidine deamin...

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Autores principales:	John F Krisko, Francisco Martinez-Torres, John L Foster, J Victor Garcia
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1ab4bdedf80242f594bece64dd402f66
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spelling	oai:doaj.org-article:1ab4bdedf80242f594bece64dd402f662021-11-18T06:05:52ZHIV restriction by APOBEC3 in humanized mice.1553-73661553-737410.1371/journal.ppat.1003242https://doaj.org/article/1ab4bdedf80242f594bece64dd402f662013-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555255/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Innate immune restriction factors represent important specialized barriers to zoonotic transmission of viruses. Significant consideration has been given to their possible use for therapeutic benefit. The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) family of cytidine deaminases are potent immune defense molecules capable of efficiently restricting endogenous retroelements as well as a broad range of viruses including Human Immunodeficiency virus (HIV), Hepatitis B virus (HBV), Human Papilloma virus (HPV), and Human T Cell Leukemia virus (HTLV). The best characterized members of this family are APOBEC3G (A3G) and APOBEC3F (A3F) and their restriction of HIV. HIV has evolved to counteract these powerful restriction factors by encoding an accessory gene designated viral infectivity factor (vif). Here we demonstrate that APOBEC3 efficiently restricts CCR5-tropic HIV in the absence of Vif. However, our results also show that CXCR4-tropic HIV can escape from APOBEC3 restriction and replicate in vivo independent of Vif. Molecular analysis identified thymocytes as cells with reduced A3G and A3F expression. Direct injection of vif-defective HIV into the thymus resulted in viral replication and dissemination detected by plasma viral load analysis; however, vif-defective viruses remained sensitive to APOBEC3 restriction as extensive G to A mutation was observed in proviral DNA recovered from other organs. Remarkably, HIV replication persisted despite the inability of HIV to develop resistance to APOBEC3 in the absence of Vif. Our results provide novel insight into a highly specific subset of cells that potentially circumvent the action of APOBEC3; however our results also demonstrate the massive inactivation of CCR5-tropic HIV in the absence of Vif.John F KriskoFrancisco Martinez-TorresJohn L FosterJ Victor GarciaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 3, p e1003242 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 John F Krisko Francisco Martinez-Torres John L Foster J Victor Garcia HIV restriction by APOBEC3 in humanized mice.
description	Innate immune restriction factors represent important specialized barriers to zoonotic transmission of viruses. Significant consideration has been given to their possible use for therapeutic benefit. The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) family of cytidine deaminases are potent immune defense molecules capable of efficiently restricting endogenous retroelements as well as a broad range of viruses including Human Immunodeficiency virus (HIV), Hepatitis B virus (HBV), Human Papilloma virus (HPV), and Human T Cell Leukemia virus (HTLV). The best characterized members of this family are APOBEC3G (A3G) and APOBEC3F (A3F) and their restriction of HIV. HIV has evolved to counteract these powerful restriction factors by encoding an accessory gene designated viral infectivity factor (vif). Here we demonstrate that APOBEC3 efficiently restricts CCR5-tropic HIV in the absence of Vif. However, our results also show that CXCR4-tropic HIV can escape from APOBEC3 restriction and replicate in vivo independent of Vif. Molecular analysis identified thymocytes as cells with reduced A3G and A3F expression. Direct injection of vif-defective HIV into the thymus resulted in viral replication and dissemination detected by plasma viral load analysis; however, vif-defective viruses remained sensitive to APOBEC3 restriction as extensive G to A mutation was observed in proviral DNA recovered from other organs. Remarkably, HIV replication persisted despite the inability of HIV to develop resistance to APOBEC3 in the absence of Vif. Our results provide novel insight into a highly specific subset of cells that potentially circumvent the action of APOBEC3; however our results also demonstrate the massive inactivation of CCR5-tropic HIV in the absence of Vif.
format	article
author	John F Krisko Francisco Martinez-Torres John L Foster J Victor Garcia
author_facet	John F Krisko Francisco Martinez-Torres John L Foster J Victor Garcia
author_sort	John F Krisko
title	HIV restriction by APOBEC3 in humanized mice.
title_short	HIV restriction by APOBEC3 in humanized mice.
title_full	HIV restriction by APOBEC3 in humanized mice.
title_fullStr	HIV restriction by APOBEC3 in humanized mice.
title_full_unstemmed	HIV restriction by APOBEC3 in humanized mice.
title_sort	hiv restriction by apobec3 in humanized mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1ab4bdedf80242f594bece64dd402f66
work_keys_str_mv	AT johnfkrisko hivrestrictionbyapobec3inhumanizedmice AT franciscomartineztorres hivrestrictionbyapobec3inhumanizedmice AT johnlfoster hivrestrictionbyapobec3inhumanizedmice AT jvictorgarcia hivrestrictionbyapobec3inhumanizedmice
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HIV restriction by APOBEC3 in humanized mice.

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