Nucleolar Localization of HIV-1 Rev Is Required, Yet Insufficient for Production of Infectious Viral Particles.

Combination antiretroviral therapy fails in complete suppression of HIV-1 due to drug resistance and persistent latency. Novel therapeutic intervention requires knowledge of intracellular pathways responsible for viral replication, specifically those untargeted by antiretroviral drugs. An understudied phenomenon is the nucleolar localization of Rev phosphoprotein, which completes nucleocytoplasmic transport of unspliced/partially spliced HIV mRNA through multimerization with intronic cis-acting targets-the Rev-response element (RRE). Rev contains a nucleolar localization signal (NoLS) comprising the COOH terminus of the arginine-rich motif for accumulation within nucleoli-speculated as the interaction ground for Rev with cellular proteins mediating mRNA-independent nuclear export and splicing. Functionality of Rev nucleolar access during HIV-1 production and infection was investigated in the context of deletion and single-point mutations within Rev-NoLS. Mutations induced upon Rev-NoLS are hypothesized to inactivate the HIV-1 infectious cycle. HIV-1HXB2 replication ceased with Rev mutations lacking nucleolar access due to loss or replacement of multiple arginine residues. Rev mutations missing single arginine residues remained strictly nucleolar in pattern and participated in proviral production, however, with reduced efficiency. Viral RNA packaging also decreased in efficiency after expression of nucleolar-localizing mutations. These results were observed during propagation of variant HIV-1NL4-3 containing nucleolar-localizing mutations within the viral backbone (M4, M5, and M6). Lentiviral particles produced with Rev single-point mutations were transducible at extremely low frequency. Similarly, HIV-1NL4-3 Rev-NoLS variants lost infectivity, unlike virulent WT (wild type) HIV-1NL4-3. HIV-1NL4-3 variants were capable of CD4+ host entry and reverse transcription as WT HIV-1NL4-3, but lacked ability to complete a full infectious cycle. We currently reveal that viral integration is deregulated in the presence of Rev-NoLS mutations

Solidity of viscous liquids II: Anisotropic flow events

Recent findings on the displacements in the surroundings of isotropic flow events in viscous liquids [Phys. Rev. E, to appear Feb. 1999] are generalized to the anisotropic case. Also, it is shown that a flow event is characterized by a dimensionless number reflecting the degree of anisotropy.Comment: Rev-tex file, no figures, submitted to Phys. Rev. E as a Brief Repor

Quantum Cryptography with Orthogonal States?

This is a Comment on Phys Rev Lett 75 (1995) 1239, by Goldenberg and VaidmanComment: 3 pages, LaTeX, 1 figure on separate page Final version in Phys Rev Lett 77 (1996) 326

Comment on Bramwell et al, "Universal Fluctuations in Correlated Systems"

This is a comment on "Universal Fluctuations in Correlated Systems", by Bramwell et al, Phys. Rev. Lett., 84, 3744 (2000.Comment: To appear in Phys. Rev. Let

Addendum: Behavior of a bipartite system in a cavity

This note is an Addendum to our previous article [Phys. Rev. A \textbf{81}, 053820 (2010)]. We show that under the assumption of a Bose-Einstein distribution for the thermal reservoir, zero-temperature properties of the entangled states considered there are not changed by heating, for temperatures up to the order of room temperatures. In this case, the system is dissipative in free space and presents stability for a small cavity, both for T=0 and for finite temperature.Comment: Revtex, 04 pages no figures, Version as accepted for publication in Phys. Rev.