Longitudinal study of HIV protease mutations in oral tissues of selected patients

Authors

  • Peter J. Hickman 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
  • Ronald B. Luftig Louisiana State University Health Sciences Center

DOI:

https://doi.org/10.20396/bjos.v3i11.8641777

Keywords:

HIV-1. Protease gene. Mutations

Abstract

Twenty-nine HIV-1 infected patients from New Orleans were enrolled as a cohort for this study over a four and one half year period. HIV-1 protease gene (pro) sequences were amplified using DNA isolated from oral tissues (gingival cuff, buccal mucosa, tongue, palate) as well as saliva and peripheral blood mononuclear cells (PBMC). PCR products were directly sequenced using a combination of manual and automated methods, and nucleotide sequences were translated using the universal genetic code. Protein sequences obtained from independent amplifications of a particular patient at a given time were consolidated into a single consensus sequence and compared to HIV-1LAI to determine amino acid replacements. The major findings were: 1) each patient had a signature sequence that probably represented the predominant HIV–1 quasispecies; 2) over periods of 19 to 1673 days mutation patterns remained relatively stable within a given patient; and 3) although nearly 40% of the initial nonsynonymous replacements in the protease signature sequences were mutations known to impart resistance to protease inhibitors (PI), over time patients did not accumulate additional PIR mutations

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Author Biographies

Janet E. Leigh, Louisiana State University Health Sciences Center

Janet is Professor and Chairman of Oral Medicine at Louisiana State University Health Sciences Center (LSUHSC). She holds a secondary appointment in the LSU School of Medicine and is on faculty at the LSUHSC School of Graduate Studies. She has received numerous awards including the Pfizer Award for Excellence in Research, Education, Patient Care and Community Outreach and the New Orleans City Business Women of the Year award.

Dr. Leigh received her B.D.S. from the University of London, and her D.M.D. from the University of Pennsylvania. She is a diplomate of the American Board of Oral Medicine and her clinical practice background includes dental care for medically complex patients in both hospital and private practice.

Her work on the development of innovative oral health-care delivery systems, HIV/AIDS clinical research, work-force issues and rural pediatric initiatives IS funded by HRSA and NIH. She serves on the Louisiana’s Governor’s Commission on HIV and AIDS and as an ambassador with the National Health Service Corps. Following Hurricane Katrina Dr Leigh spearheaded the efforts to re-establish dental services in New Orleans while the LSU Dental School was temporarily relocated to Baton Rouge. Her work focuses on access to care issues and expansion of the dental safety net, funding of research and care delivery, development of clinical practice boundaries in cross-discipline collaboration, development of future healthcare work-force and education of that work-force in a culturally appropriate manner.

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).

References

Barrie KA, Perez EE, Lamers SL, Farmerie WG, Dunn BM, Sleasman JW et al. Natural variation in HIV-1 protease, Gag p7 and p6, and protease cleavage sites within Gag/Pol polyproteins: amino acid substitutions in the absence of protease inhibitors in mothers and children infected by human immunodeficiency virus type 1. Virology 1996; 219: 407-16.

Hickman PJ, Leigh JE, Mera RM, Fidel PL Jr, Luftig RB. Oropharyngeal candidiasis in HIV+ patients may influence the selection of HIV-1 protease variants. Virus Res 2002; 87: 97-106.

Hickman PJ, Mera RM, Leigh JE, Fidel PL Jr, Mock AR, Gallaher WR et al. Specific protease mutation patterns are associated with oropharyngeal candidiasis in a New Orleans patient cohort of HIV-infected individuals. Braz J Oral Sci 2004; 3: 446-53.

Greenspan JC, Barr CE, Sciubba JJ, Winkler JR. Oral manifestations of HIV infection: definitions, diagnostic criteria and principles of therapy. Oral Surg Oral Med Oral Pathol 1992; 73: 142-4.

Telesnitsky A and Goff SP. Reverse transcriptase and the generation of retroviral DNA. In: Coffin JM, Hughes SH, Varmus HE. Editors. Retroviruses. New York: Cold Spring Harbor Laboratory Press; 1997. p.141-4.

Myers G, Wain-Hobson S, Henderson L, Korber B, Jeang K, Pavlakis G. Human retroviruses and AIDS. Sequence bank. Los Alamos, New Mexico: Los Alamos National Laboratory; 1995.

Bradac J, Rock K, Thakallapally R, Gaschen B, Pillai S, Rese P et al. Nucleotide alignments of HIV-1/SIVcpz complete genomes. In: Kuiken C, Foley B, Hahn B, et al. Editors. Human retroviruses and AIDS. Los Alamos, New Mexico: Theoretical Biology and Biophysics, Group T-10, Mail Stop K710, Los Alamos National Laboratory; 1999. p.75-81.

Gallaher WR, Ball JM, Garry RF, Martin-Amedee AM, Montelaro RC. A general model for the surface glycoproteins of HIV and other retroviruses. AIDS Res Hum Retroviruses 1995; 11: 191- 202.

Ogden RC, Flexner CW. Editors. Protease inhibitors in AIDS therapy. New York: Marcel Dekker; 2001.

Shugars DC Wahl SM. The role of the oral environment in HIV- 1 transmission. J Am Dent Assoc 1998; 129: 851-8.

Wahl SM, Worley P, Jin WW. Secretory leukocyte protease inhibitor (SLPI) in mucosal fluids inhibits HIV-1. Oral Dis 1997; 3(suppl): 564-9.

Archibald DW Cole GA. In vitro inhibition of HIV-1 infectivity by human salivas. AIDS Res Hum Retroviruses 1990; 6: 1425-32.

Chun TW, Stuyver L, Mizell SB, Ehler JA, Micon M, Baseler AL et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci USA 1997; 94: 13193-7.

Smith TF, Srinivasan A, Schochetman G. The phylogenetic history of immunodeficiency viruses. Nature 1988; 333: 573-5.

Downloads

Published

2015-11-17

How to Cite

1.
Hickman PJ, Leigh JE, Fidel. Jr PL, Luftig RB. Longitudinal study of HIV protease mutations in oral tissues of selected patients. Braz. J. Oral Sci. [Internet]. 2015 Nov. 17 [cited 2023 Feb. 5];3(11):615-8. Available from: https://periodicos.sbu.unicamp.br/ojs/index.php/bjos/article/view/8641777

Issue

Section

Article

Most read articles by the same author(s)