Inhibitory Activities of Three Classes of Acyclic Nucleoside Phosphonates against Murine Polyomavirus and Primate Simian Virus 40 Strains

ABSTRACT Murine polyomavirus and simian virus 40 were used to evaluate the potencies of the compounds of three classes of acyclic nucleoside phosphonates: (i) the original HPMP (3-hydroxy-2-phosphonomethoxypropyl) and PME (2-phosphonomethoxyethyl) derivatives, (ii) the 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidine (DAPy) derivatives, and (iii) a new class of HPMP derivatives containing a 5-azacytosine moiety. The last class showed the highest activities and selectivities against both polyomaviruses.

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A NEW CLASS OF ACYCLIC NUCLEOSIDE PHOSPHONATES: SYNTHESIS AND BIOLOGICAL ACTIVITY OF 9-{[(PHOSPHONOMETHYL)AZIRIDIN-1-YL]METHYL}GUANINE (PMAMG) AND ANALOGUES

Nucleosides Nucleotides & Nucleic Acids ◽

10.1081/ncn-120015721 ◽

2002 ◽

Vol 21 (10) ◽

pp. 619-635 ◽

Cited By ~ 16

Author(s):

Ghassan Abu Sheikha ◽

Paolo La Colla ◽

Anna Giulia Loi

Keyword(s):

Biological Activity ◽

New Class ◽

Acyclic Nucleoside Phosphonates ◽

Acyclic Nucleoside

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Early Steps of Polyomavirus Entry into Cells

Journal of Virology ◽

10.1128/jvi.74.18.8582-8588.2000 ◽

2000 ◽

Vol 74 (18) ◽

pp. 8582-8588 ◽

Cited By ~ 54

Author(s):

Joanna M. Gilbert ◽

Thomas L. Benjamin

Keyword(s):

Jc Virus ◽

Simian Virus 40 ◽

Simian Virus ◽

Dominant Negative ◽

Independent Manner ◽

Caveolin 1 ◽

Dominant Negative Form ◽

Murine Polyomavirus ◽

Dynamin I ◽

Negative Form

ABSTRACT The mechanism by which murine polyomavirus penetrates cells and arrives at the nucleus, the site of viral replication, is not well understood. Simian virus 40 and JC virus, two closely related members of the polyomavirus subfamily, use caveola- and clathrin-mediated uptake pathways for entry, respectively. The data presented here indicate that compounds that block endocytosis of both caveola- and clathrin-derived vesicles have no effect on polyomavirus infectivity. Polyomavirus does not appear to colocalize with either clathrin light chain or caveolin-1 by immunofluorescence microscopy. Additionally, expression of a dominant-negative form of dynamin I has no effect on polyomavirus uptake and infectivity. Therefore, polyomavirus uptake occurs through a class of uncoated vesicles in a clathrin-, caveolin-1-, and dynamin I-independent manner.

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Cell Penetration and Trafficking of Polyomavirus

Journal of Virology ◽

10.1128/jvi.77.4.2615-2622.2003 ◽

2003 ◽

Vol 77 (4) ◽

pp. 2615-2622 ◽

Cited By ~ 48

Author(s):

Joanna M. Gilbert ◽

Ilya G. Goldberg ◽

Thomas L. Benjamin

Keyword(s):

Actin Filaments ◽

Simian Virus 40 ◽

Simian Virus ◽

Endocytic Pathway ◽

Dynamic State ◽

Cell Penetration ◽

Stabilizing Agents ◽

Virus Particles ◽

Murine Polyomavirus ◽

Microfilament System

ABSTRACT The murine polyomavirus (Py) enters mouse fibroblasts and kidney epithelial cells via an endocytic pathway that is caveola-independent (as well as clathrin-independent). In contrast, uptake of simian virus 40 into the same cells is dependent on caveola. Following the initial uptake of Py, both microtubules and microfilaments play roles in trafficking of the virus to the nucleus. Colcemid, which disrupts microtubules, inhibits the ability of Py to reach the nucleus and replicate. Paclitaxel, which stabilizes microtubules and prevents microtubule turnover, has no effect, indicating that intact but not dynamic microtubules are required for Py infectivity. Compounds that disrupt actin filaments enhance Py uptake while stabilization of actin filaments impedes Py infection. Virus particles are seen in association with actin in cells treated with microfilament-disrupting or filament-stabilizing agents at levels comparable to those in untreated cells, suggesting that a dynamic state of the microfilament system is important for Py infectivity.

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