Internists, Infectious Disease Specialist (virus, bacteria, parasites)
10 years of experience

Accepting new patients
Greater Philadelphia Health Action Inc.
432 N 6th St
North Philadelphia East, Philadelphia, PA 19123
Locations and availability (6)

Education ?

Medical School Score Rankings
University of Wisconsin at Madison (2000)
  • Currently 4 of 4 apples
Top 25%

Publications & Research

Dr. Mahnke has contributed to 4 publications.
Title Analysis of Hiv-2 Vpx by Modeling and Insertional Mutagenesis.
Date June 2006
Journal Virology

Vpx facilitates HIV-2 nuclear localization by a poorly understood mechanism. We have compared Vpx to an NMR structure HIV-1 Vpr in a central helical domain and probed regions of Vpx by insertional mutagenesis. A predicted loop between helices two and three appears to be unique, overlapping with a known novel nuclear localization signal. Overall, Vpx was found to be surprisingly flexible, tolerating a series of large insertions. We found that insertion within the polyproline-containing C-terminus destabilizes nuclear localization, whereas mutating a second helix in the central domain disrupts viral packaging. Other insertional mutants in the predicted loop and in a linker region between the central domain and the C-terminus may be useful as sites of intramolecular tags as they could be packaged adequately and retained preintegration complex associated integration activity in a serum starvation assay. An unexpected result was found within a previously defined nuclear localization motif near aa 71. This mutant retained robust nuclear localization in a GFP fusion assay and was competent for preintegration complex associated nuclear import. In summary, we have modeled helical content in Vpx and assessed potential sites of intramolecular tags which may prove useful for protein-protein interactions studies.

Title Conserved Amino Acids of the Human Immunodeficiency Virus Type 2 Vpx Nuclear Localization Signal Are Critical for Nuclear Targeting of the Viral Preintegration Complex in Non-dividing Cells.
Date April 2006
Journal Virology

The HIV-2 viral accessory protein Vpx is related to, but distinct from the Vpr protein of HIV-1. Vpx is packaged into virions and as a component of the viral preintegration complex (PIC) is required for efficient virus replication in non-dividing cells. We have previously reported that the minimal transferable region of Vpx that contained karyophilic properties was aa 65 to 72. Analysis of Vpx sequences from various HIV-2/SIV strains reveals that this region contains highly conserved amino acids, including two basic residues (K68, R70) and three tyrosines (Y66, Y69, Y71). Here, we demonstrate that mutation of the basic or tyrosine residues abolishes PIC nuclear import in arrested cells as assessed by PCR detection of viral integration. Examination of cell-free virus by Western blot indicated that all mutant proteins were incorporated into virions, suggesting that the lack of replication in arrested cells was not due to a loss of Vpx in target cells. Together, these studies map critical residues of the Vpx nuclear localization signal that are required for efficient infection of non-dividing cells.

Title Tn5: A Molecular Window on Transposition.
Date February 2000
Journal Biochemical and Biophysical Research Communications

DNA transposition is an underlying process involved in the remodeling of genomes in all types of organisms. We analyze the multiple steps in cut-and-paste transposition using the bacterial transposon Tn5 as a model. This system is particularly illuminating because of the existence of structural, genetic, and biochemical information regarding the two participating specific macromolecules: the transposase and the 19-bp sequences that define the ends of the transposon. However, most of the insights should be of general interest because of similarities to other transposition-like systems such as HIV-1 DNA integration into the host genome.

Title Aberrant S(rn)1 Reaction of 4-aminophenol with Alpha,p-dinitrocumene: Epr Observation of Intermediates.
Journal Organic Letters

The tert-butoxide-induced substitution of alpha,p-dinitrocumene by 4-aminophenol unexpectedly afforded the N-coupled product, 2-(4-hydroxyanilino)-2-(4-nitrophenyl)propane. EPR observations revealed arylaminyl radical intermediates as well as coupled anion radicals, hence the normal S(RN)1 process may compete with an alternative nonchain reaction pathway.

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