NDLI: Rodent Cells Support Key Functions of the Human Immunodeficiency Virus Type 1 Pathogenicity Factor Nef

Content Provider	PubMed Central
Author	Keppler, Oliver T. Ina, Allespach Schüller, Lismarie David, Fenard Greene, Warner C. Fackler, Oliver T.
Copyright Year	2005
Abstract	After infection with human immunodeficiency virus (HIV), progression toward immunodeficiency is governed by a complex interplay of viral and host determinants. The viral accessory protein Nef is a key factor for the development of AIDS. Strains of HIV and simian immunodeficiency virus that lack functional nef genes either do not induce AIDS or do so only after a significant delay. The validity of a transgenic-small-animal model for de novo infection by HIV will depend on its ability to recapitulate the actions of critical factors of viral pathogenicity, such as Nef. We assessed the ability of rat, mouse, and hamster cells to support key effector functions of Nef. In cell lines from rodents, the subcellular distribution of wild-type HIV type 1 strain SF2 Nef and mutants was comparable to that in human cells. Nef downregulated human CD4 from the cell surface, was associated with p21-activated kinase activity, and enhanced the infectivity of HIV-1 virions. Importantly, these Nef-induced effects, as well as the downregulation of rat CD4 and major histocompatibility complex class I molecules, could also be demonstrated in primary T lymphocytes and macrophages from human CD4-transgenic rats. Thus, HIV-1 Nef exerts key functions in rodent cells. In line with our ongoing efforts to establish a transgenic-rat model of HIV disease, these results indicate that important aspects of viral pathogenesis could be addressed in a transgenic-rodent model permissive for de novo infection and that such a model would be valuable for evaluating the function of Nef in vivo.
Related Links	http://dx.doi.org/10.1128/jvi.79.3.1655-1665.2005
Ending Page	1665
Page Count	11
Starting Page	1655
File Format	PDF
ISSN	0022538X
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	3
Volume Number	79
Language	English
Publisher	American Society for Microbiology
Publisher Date	2005-02-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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Dynamic Evolution of the Human Immunodeficiency Virus Type 1 Pathogenic Factor, Nef†

Requirement of human immunodeficiency virus type 1 nef for in vivo replication and pathogenicity.

Primary Human Immunodeficiency Virus Type 1 Nef Alleles Show Major Differences in Pathogenicity in Transgenic Mice▿

Modulation of Different Human Immunodeficiency Virus Type 1 Nef Functions during Progression to AIDS

Human Immunodeficiency Virus Type 1 Nef Functions at the Level of Virus Entry by Enhancing Cytoplasmic Delivery of Virions

Functional Characterization of the Human Immunodeficiency Virus Type 1 Nef Acidic Domain▿

Dissociation of the CD4 downregulation and viral infectivity enhancement functions of human immunodeficiency virus type 1 Nef.

The Human Immunodeficiency Virus Type 1 nef Gene Can to a Large Extent Replace Simian Immunodeficiency Virus nef In Vivo

Association of Nef with the Human Immunodeficiency Virus Type 1 Core

Rodent Cells Support Key Functions of the Human Immunodeficiency Virus Type 1 Pathogenicity Factor Nef

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Dynamic Evolution of the Human Immunodeficiency Virus Type 1 Pathogenic Factor, Nef†

Requirement of human immunodeficiency virus type 1 nef for in vivo replication and pathogenicity.

Primary Human Immunodeficiency Virus Type 1 Nef Alleles Show Major Differences in Pathogenicity in Transgenic Mice▿

Modulation of Different Human Immunodeficiency Virus Type 1 Nef Functions during Progression to AIDS

Human Immunodeficiency Virus Type 1 Nef Functions at the Level of Virus Entry by Enhancing Cytoplasmic Delivery of Virions

Functional Characterization of the Human Immunodeficiency Virus Type 1 Nef Acidic Domain▿

Dissociation of the CD4 downregulation and viral infectivity enhancement functions of human immunodeficiency virus type 1 Nef.

The Human Immunodeficiency Virus Type 1 nef Gene Can to a Large Extent Replace Simian Immunodeficiency Virus nef In Vivo

Association of Nef with the Human Immunodeficiency Virus Type 1 Core

Rodent Cells Support Key Functions of the Human Immunodeficiency Virus Type 1 Pathogenicity Factor Nef