APOBEC3G-independent reduction in virion infectivity during long-term HIV-1 replication in terminally differentiated macrophages

Miyagi, Eri; Schwartzkopff, Franziska; Plishka, Ronald J.; Buckler-White, Alicia; Clouse, Kathleen A.; Strebel, Klaus

doi:10.1016/j.virol.2008.06.033

Cited by 12 publications

(15 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To analyze the effects of Vpu on Bst-2 expression under more physiological conditions, we compared Bst-2 levels of uninfected MDM with those infected for 24 days with HIV-1 Ada as described in ref. 34. Consistent with the results from HeLa cells, we noted a reduction of endogenous Bst-2 levels (Fig.…”

Section: Hiv-1 Vpu Enhances the Release Of Virions From Infected Cellssupporting

confidence: 91%

See 1 more Smart Citation

Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

Miyagi

Andrew

Kao

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

206

281

View full text Add to dashboard Cite

HIV-1 Vpu enhances the release of virions from infected cells. Recent work identified Bst-2/CD317/tetherin as a host factor whose inhibitory activity on viral release is counteracted by Vpu. A current working model proposes that Bst-2 inhibits virus release by tethering viral particles to the cell surface. Here, we analyzed endogenous Bst-2 with respect to its effect on virus release from HeLa cells, T cells, and macrophages. We noted significant cell type-dependent variation in Bst-2 expression. Vpu caused a reduction in Bst-2 expression in transfected HeLa cells and long-term infected macrophages. However, Vpu expression did not result in cell surface down-modulation of Bst-2 or a reduction in intracellular Bst-2 expression in CEMx174 or H9 cells, yet virus replication in these cells was Vpu-responsive. Surprisingly, Bst-2 was undetectable in cell-free virions that were recovered from the surface of HeLa cells by physical shearing, suggesting that a tethering model may not explain all of the functional properties of Bst-2. Taken together we conclude that enhancement of virus release by Vpu does not, at least in CEMx174 and H9 cells, require cell surface down-modulation or intracellular depletion of Bst-2, nor does it entail exclusion of Bst-2 from viral particles.

show abstract

Section: Hiv-1 Vpu Enhances the Release Of Virions From Infected Cellssupporting

confidence: 91%

“…40 to allow differentiation into MDM as reported in ref. 34. IFN␣-2c was added as indicated in the text and detailed in SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

Miyagi

Andrew

Kao

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

206

281

View full text Add to dashboard Cite

show abstract

“…Elutriated monocytes from healthy donors were allowed to differentiate into macrophages in six-well plates (4 ϫ 10 6 per well) in 2 ml of complete DMEM containing10% pooled human serum for 7 days (35). The cells were then treated with alpha 2c interferon (IFN-␣2c; 0 to 10 ng/ml) for 24 h and analyzed for protein expression and mRNA levels by immunoblotting or Northern blot analysis, respectively.…”

Section: Methodsmentioning

confidence: 99%

Stably Expressed APOBEC3F Has Negligible Antiviral Activity

Miyagi

Brown

Opi

et al. 2010

J Virol

Self Cite

View full text Add to dashboard Cite

APOBEC3F (A3F) is a member of the family of cytidine deaminases that is often coexpressed with APOBEC3G (A3G) in cells susceptible to HIV infection. A3F has been shown to have strong antiviral activity in transient-expression studies, and together with A3G, it is considered the most potent cytidine deaminase targeting HIV. Previous analyses suggested that the antiviral properties of A3F can be dissociated from its catalytic deaminase activity. We were able to confirm the deaminase-independent antiviral activity of exogenously expressed A3F; however, we also noted that exogenous expression was associated with very high A3F mRNA and protein levels. In analogy to our previous study of A3G, we produced stable HeLa cell lines constitutively expressing wild-type or deaminase-defective A3F at levels that were more in line with the levels of endogenous A3F in H9 cells. A3F expressed in stable HeLa cells was packaged into Vif-deficient viral particles with an efficiency similar to that of A3G and was properly targeted to the viral nucleoprotein complex. Surprisingly, however, neither wild-type nor deaminase-defective A3F inhibited HIV-1 infectivity. These results imply that the antiviral activity of endogenous A3F is negligible compared to that of A3G.

show abstract

“…These RFs include APOBEC3 [35], sterile alpha motif (SAM) domain and HD domain-containing protein 1 (SAMHD1) [36] and the recently identified MX2 (myxovirus resistance 2, also called MXB) [37]. APOBEC3 plays an important role in triggering G to A hypermutation of HIV-1 genome (Figure 1).…”

Section: General Mechanisms Of Latencymentioning

confidence: 99%

HIV-1 Latency in Monocytes/Macrophages

Kumar

Abbas

Herbein

2014

Viruses

183

198

View full text Add to dashboard Cite

Human immunodeficiency virus type 1 (HIV-1) targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART) has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

show abstract

APOBEC3G-independent reduction in virion infectivity during long-term HIV-1 replication in terminally differentiated macrophages

Cited by 12 publications

References 50 publications

Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

Stably Expressed APOBEC3F Has Negligible Antiviral Activity

HIV-1 Latency in Monocytes/Macrophages

Contact Info

Product

Resources

About