Specific protease mutation patterns are associated with oropharyngeal candidiasis in a New Orleans patient cohort of HIV-infected individuals

Authors

  • Peter J. Hickman Louisiana State University Health Sciences Center
  • Robertino M. Mera Louisiana State University Health Sciences Center
  • Janet E. Leigh Louisiana State University Health Sciences Center
  • Paul L. Fidel Jr Louisiana State University Health Sciences Center
  • Allen R. Mock Louisiana State University Health Sciences Center
  • William R. Gallaher Louisiana State University Health Sciences Center
  • Ronald B. Luftig Louisiana State University Health Sciences Center

DOI:

https://doi.org/10.20396/bjos.v3i9.8641746

Keywords:

HIV-1. Mutation. Proteases. Candidiasis

Abstract

HIV-1 protease gene sequences were obtained from peripheral blood, saliva or oral tissues of 35 HIV+ patients using nested amplification and manual sequencing of PCR products. Of the 35 HIV+ patients 9 had clinical oropharyngeal candidiasis (OPC) while 26 did not, and only 4 patients were on protease inhibitor (PI) therapy. These patients were collected prior to major use of HAART therapy in New Orleans, Louisiana. Analysis of 172 amino acid sequences revealed unique patterns of mutation that were in most cases independent of the type of cell from which DNA was isolated and were, instead, primarily dependent on the individual patient. Principal component analysis indicated that approximately 50% of the variance of the amino acid replacements could be explained by patterns of change seen in only five patients. Significantly, 4 of these 5 patients were OPC+ indicating that patients with OPC are more likely to express a principal mutation pattern than patients without OPC (p = 0.002, Chi square). Dendrograms revealed that these five patients clustered separately from each other and from HIV-1LAI suggesting that principal mutation patterns as well as OPC are independent of viral evolution. In conclusion, prior to widespread use of PI therapy to combat HIV-1, patients with OPC exhibited unique patterns of amino acid replacements within the HIV-1 protease.

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Author Biographies

Janet E. Leigh, Louisiana State University Health Sciences Center

 Janet Leigh, BDS, DMD, Chair of the Department of Oral Medicine and Radiology at LSU Health Sciences Center New Orleans School of Dentistry, is one of ten Health Policy Fellows selected by the Robert Wood Johnson Foundation® (RWJF) for 2009-10. She is the first dentist to be selected since 1999. The award comes with a grant in the amount of $165,000 for the residential stay, travel, research, conferences, and other leadership development activities.

Paul L. Fidel Jr, Louisiana State University Health Sciences Center

Dr. Fidel received his Bachelor of Science degree in Biology from Allegheny College in Pennsylvania in 1984. He then received his Master of Science and PhD degrees in Microbiology from the University of Oklahoma in 1987 and 1988, respectively. Dr. Fidel conducted postdoctoral training in the lab of Dov Boros in the Department of Immunology and Microbiology at Wayne State University School of Medicine in Detroit. He accepted a position of Assistant Professor in the Division of Infectious Diseases, Department of Internal Medicine, Wayne State University School of Medicine in 1990. Dr. Fidel came to LSUHSC in 1995 as an Associate Professor in the Department of Microbiology, Immunology, and Parasitology. He was promoted to Professor in 1999 and named the Carl Baldridge Research Professor and Director of the Center of Excellence in Oral and Craniofacial Biology, Associate Dean for Research in 2001.
 

Ronald B. Luftig, Louisiana State University Health Sciences Center

The Luftig laboratory is currently involved in the 
following research:

-A vaccine has been issued for HIV-1 based on prophylaxis with killed protease defective immature particles Patent with Immune Response Corporation).

-Biodepuration of Vibrio vulnificus from raw oysters using a unique Mr: 22,000 protein and a sentinel study of HEV in clams captured from Lake Pontchartrain (In collaboration with Drs. William Pelon and Kenneth Johnston, funded by NOAA).
-Gene therapy using enteric Adenovirus 41 as a gutless vector to deliver genes to intestinal regions (patent issued for Dr. Luftig; collaboration with Dr. Jay Kolls and the Gene Therapy Group).

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Published

2015-11-16

How to Cite

1.
Hickman PJ, Mera RM, Leigh JE, Fidel Jr PL, Mock AR, Gallaher WR, Luftig RB. Specific protease mutation patterns are associated with oropharyngeal candidiasis in a New Orleans patient cohort of HIV-infected individuals. Braz. J. Oral Sci. [Internet]. 2015 Nov. 16 [cited 2022 Dec. 1];3(9):445-53. Available from: https://periodicos.sbu.unicamp.br/ojs/index.php/bjos/article/view/8641746

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