Novel tetra-peptide insertion in Gag-p6 ALIX-binding motif in HIV-1 subtype C associated with protease inhibitor failure in Indian patients

Ujjwal Neogi; Shwetha D Rao; Irene Bontell; Jens Verheyen; Vasudev R Rao; Sagar C Gore; Neelesh Soni; Anita Shet; Eugen Schülter; Maria L Ekstrand; Amogne Wondwossen; Rolf Kaiser; Mallur S Madhusudhan; Vinayaka R Prasad; Anders Sonnerborg

doi:10.1097/QAD.0000000000000419

Novel tetra-peptide insertion in Gag-p6 ALIX-binding motif in HIV-1 subtype C associated with protease inhibitor failure in Indian patients

AIDS. 2014 Sep 24;28(15):2319-22. doi: 10.1097/QAD.0000000000000419.

Authors

Ujjwal Neogi¹, Shwetha D Rao, Irene Bontell, Jens Verheyen, Vasudev R Rao, Sagar C Gore, Neelesh Soni, Anita Shet, Eugen Schülter, Maria L Ekstrand, Amogne Wondwossen, Rolf Kaiser, Mallur S Madhusudhan, Vinayaka R Prasad, Anders Sonnerborg

Affiliation

¹ aDivision of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden bDivision of Public Health and Infection, St. John's Research Institute, Bangalore India cUnit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden dInstitute of Virology, University-Hospital, University Duisburg-Essen, Essen, Germany eDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA fIndian Institute of Science Education and Research, Pune, Maharashtra, India gInstitute of Virology, University of Cologne, Cologne, Germany hDepartment of Medicine, University of California, San Francisco, California, USA iDepartment of Medicine, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia jBioinformatics Institute kDepartment of Biological Sciences, National University of Singapore, Singapore.

Abstract

A novel tetra-peptide insertion was identified in Gag-p6 ALIX-binding region, which appeared in protease inhibitor failure Indian HIV-1C sequences (odds ratio=17.1, P < 0.001) but was naturally present in half of untreated Ethiopian HIV-1C sequences. The insertion is predicted to restore ALIX-mediated virus release pathway, which is lacking in HIV-1C. The clinical importance of the insertion needs to be evaluated in HIV-1C dominating regions wherein the use of protease inhibitor drugs are being scaled up.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cohort Studies
Drug Resistance, Viral*
Female
Genotype
HIV Infections / drug therapy*
HIV Infections / virology*
HIV Protease Inhibitors / therapeutic use*
HIV-1 / classification
HIV-1 / genetics*
HIV-1 / isolation & purification
Humans
India
Male
Middle Aged
Mutagenesis, Insertional*
Treatment Failure
gag Gene Products, Human Immunodeficiency Virus / genetics*

Substances

HIV Protease Inhibitors
gag Gene Products, Human Immunodeficiency Virus
p6 gag protein, Human immunodeficiency virus 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding