Abstract
Recent discoveries have revealed previously unappreciated complexity with which retroviruses interact with their hosts. In particular, we have become aware that many mammals, including humans, are equipped with genes encoding so-called "restriction factors," that provide considerable resistance to retroviral infection. Such antiretroviral genes are sometimes constitutively expressed, and sometimes interferon-induced. Thus they can be viewed as comprising an intrinsic immune system that provides a pre-mobilized defense against retroviral infection or, alternatively, as a specialized extension of conventional innate immunity. Antiretroviral restriction factors have evolved at an unusually rapid pace, particularly in primates, and some startling examples of evolutionary change are present in genes encoding restriction factors. Our understanding of the mechanisms by which restriction factors interfere with retroviral replication, and how their effects are avoided by certain retroviruses, is accruing, but far from complete. Such knowledge could allow for novel forms of therapeutic intervention in pathogenic retroviral infections, as well as the development of animal models of human disease.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
APOBEC Deaminases
-
Animals
-
Antigens, CD / immunology
-
Antigens, CD / metabolism
-
Antiviral Restriction Factors
-
Carrier Proteins / immunology
-
Carrier Proteins / metabolism
-
Cytidine Deaminase
-
Cytosine Deaminase / immunology
-
Cytosine Deaminase / metabolism
-
Evolution, Molecular
-
GPI-Linked Proteins
-
HIV / pathogenicity
-
HIV / physiology*
-
HIV Infections / genetics
-
HIV Infections / immunology*
-
HIV Infections / virology*
-
Humans
-
Immunity, Innate
-
Interferons / genetics
-
Interferons / immunology*
-
Interferons / metabolism
-
Membrane Glycoproteins / immunology
-
Membrane Glycoproteins / metabolism
-
Transcriptional Activation
-
Tripartite Motif Proteins
-
Ubiquitin-Protein Ligases
-
Virulence
-
Virus Assembly
-
vif Gene Products, Human Immunodeficiency Virus / immunology
-
vif Gene Products, Human Immunodeficiency Virus / metabolism*
Substances
-
Antigens, CD
-
Antiviral Restriction Factors
-
BST2 protein, human
-
Carrier Proteins
-
GPI-Linked Proteins
-
Membrane Glycoproteins
-
Tripartite Motif Proteins
-
vif Gene Products, Human Immunodeficiency Virus
-
Interferons
-
TRIM5 protein, human
-
Ubiquitin-Protein Ligases
-
Cytosine Deaminase
-
APOBEC Deaminases
-
APOBEC3 proteins, human
-
Cytidine Deaminase