scholarly journals Partial Inhibition of Human Immunodeficiency Virus Replication by Type I Interferons: Impact of Cell-to-Cell Viral Transfer

2009 ◽  
Vol 83 (20) ◽  
pp. 10527-10537 ◽  
Author(s):  
Daniela Vendrame ◽  
Marion Sourisseau ◽  
Virginie Perrin ◽  
Olivier Schwartz ◽  
Fabrizio Mammano
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Type I Interferons ◽  
Human Immunodeficiency Virus Replication ◽  
Type I ◽  
Restriction Factors ◽  
Hiv Replication ◽  
Potent Effect ◽  
Immunodeficiency Virus ◽  
The Impact

ABSTRACT Type I interferons (IFN) inhibit several steps of the human immunodeficiency virus type 1 (HIV) replication cycle. Some HIV proteins, like Vif and Vpu, directly counteract IFN-induced restriction factors. Other mechanisms are expected to modulate the extent of IFN inhibition. Here, we studied the impact of IFN on various aspects of HIV replication in primary T lymphocytes. We confirm the potent effect of IFN on Gag p24 production in supernatants. Interestingly, IFN had a more limited effect on HIV spread, measured as the appearance of Gag-expressing cells. Primary isolates displayed similar differences in the inhibition of p24 release and virus spread. Virus emergence was the consequence of suboptimal inhibition of HIV replication and was not due to the selection of resistant variants. Cell-to-cell HIV transfer, a potent means of virus replication, was less sensitive to IFN than infection by cell-free virions. These results suggest that IFN are less active in cell cultures than initially thought. They help explain the incomplete protection by naturally secreted IFN during HIV infection and the unsatisfactory outcome of IFN treatment in HIV-infected patients.

Metabolism of 3′-Azido-3′-Deoxythymidine and 3′-Fluoro-3′-Deoxythymidine in Combination in Human Immunodeficiency Virus Infected Lymphoblastoid Cells

1992 ◽  
Vol 3 (3) ◽  
pp. 165-170 ◽  
Author(s):  
S. Cox
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Cell Types ◽  
Human Immunodeficiency Virus Replication ◽  
Lymphoblastoid Cells ◽  
Synergistic Inhibition ◽  
Immunodeficiency Virus ◽  
Deoxynucleoside Triphosphate ◽  
The Individual

A combination of 3′-azido-3′-deoxythymidine (AZT) with 3′-fluoro-3′-deoxythymidine (FLT) has been shown previously to give synergistic inhibition of human immunodeficiency virus replication and greatly reduced cytotoxicity in vitro. The phosphorylation of the compounds, and their effect upon the natural deoxynucleoside triphosphate pools, were compared in CEM, H9, and HIV-infected H9 lymphoblastoid cells, both for the compounds when used alone and when combined together. Higher levels of FLT triphosphate than AZT triphosphate, and higher levels of AZT monophosphate than FLT monosphosphate, were formed in all cell types. Both compounds were phosphorylated most efficiently in CEM cells, whereas they were least efficiently phosphorylated in infected H9 cells. Owing to competition, the phosphorylation of both analogues was reduced when used in combination, compared to the phosphorylation of the separate compounds. The phosphorylation of the separate compounds was therefore at a maximum and was not increased by combining the compounds. The two compounds competed equally with each other for phosphorylation when used at a ratio of AZT: FLT of 5: 1. Both analogues severely reduced the deoxynucleoside triphosphate pools in uninfected and human immunodeficiency virus-infected H9 cells, but not in CEM cells. The effects of the two compounds were similar to those found when the compounds were combined, and thus H9 cells were shown to be much more sensitive to the effects of the analogues upon deoxynucleoside triphosphate pools than CEM cells were. Thus the synergistic combination of 3′-azido-3′-deoxythymidine and 3′-fluoro-3′-deoxythymidine was shown to have a similar metabolism and a similar effect upon cellular deoxynucleoside triphosphate pools to the individual compounds.

scholarly journals Interplay between Intrinsic and Innate Immunity during HIV Infection

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 922 ◽  
Author(s):  
Louis Bergantz ◽  
Frédéric Subra ◽  
Eric Deprez ◽  
Olivier Delelis ◽  
Clémence Richetta
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Hiv Infection ◽  
Type I ◽  
Restriction Factors ◽  
Intrinsic Immunity ◽  
First Line ◽  
Hiv Replication ◽  
Interferon Stimulated Genes ◽  
Immunodeficiency Virus

Restriction factors are antiviral components of intrinsic immunity which constitute a first line of defense by blocking different steps of the human immunodeficiency virus (HIV) replication cycle. In immune cells, HIV infection is also sensed by several pattern recognition receptors (PRRs), leading to type I interferon (IFN-I) and inflammatory cytokines production that upregulate antiviral interferon-stimulated genes (ISGs). Several studies suggest a link between these two types of immunity. Indeed, restriction factors, that are generally interferon-inducible, are able to modulate immune responses. This review highlights recent knowledge of the interplay between restriction factors and immunity inducing antiviral defenses. Counteraction of this intrinsic and innate immunity by HIV viral proteins will also be discussed.

scholarly journals Loss of CD4 membrane expression and CD4 mRNA during acute human immunodeficiency virus replication.

1988 ◽  
Vol 168 (6) ◽  
pp. 1953-1969 ◽  
Author(s):  
P Salmon ◽  
R Olivier ◽  
Y Riviere ◽  
E Brisson ◽  
J C Gluckman ◽  
...  
Keyword(s):  
Cell Surface ◽  
Virus Replication ◽  
Receptor Gene ◽  
Human Immunodeficiency Virus Replication ◽  
Hiv Replication ◽  
Membrane Expression ◽  
Receptor Modulation ◽  
Immunodeficiency Virus ◽  
Vaccinia Viruses ◽  
Hiv Envelope

Using mAbs and genomic probe to the CD4 molecule, the HIV receptor, we demonstrated that HIV replication induces the disappearance of its functional receptor from the cell surface by two distinct mechanisms. First, after being expressed onto the cell surface, HIV envelope gp110 will complex CD4, efficiently masking the CD4 epitope used by the virus to bind its receptor. This phenomenon occurs on the surface of each infected cell and is not due to the release of soluble gp110; infection with recombinant HIV/vaccinia viruses expressing a mutated HIV env gene designed to prevent gp110 release from the cell surface induces a similar gp/CD4 complexes formation. Second, virus replication induces a dramatic and rapid loss of CD4 mRNA transcripts, preventing new CD4 molecules from being synthesized. These two mechanisms of receptor modulation could have been developed to avoid reinfection of cells replicating the virus as well as to produce more infectious particles. These results suggest that the classical virus interference documented for other retroviruses might not only be due to receptor/envelope interaction, but might also depend on receptor gene expression.

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