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Investigation of Viral Genetic and Biologic Determinants of HIV-1 Subtype C Predominance in India

Rodriguez, Milka Alejandra (2007) Investigation of Viral Genetic and Biologic Determinants of HIV-1 Subtype C Predominance in India. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

In India, HIV-1 subtype C has been the predominant subtype throughout the course of the HIV-1 epidemic, regardless of geographic region in the country. We hypothesize that the dominance of HIV-1 subtype C compared to other subtypes in India is due to enhanced replication fitness and/or enhanced transmission efficiency of this subtype across the mucosal surface over other subtypes present in India. The specific aims of this project are: (1) to compare the replication fitness between Indian HIV-1 subtype A and subtype C; (2) to evaluate the transmission efficiency of Indian HIV-1 subtype A and subtype C across the mucosa of cervical tissue; and (3) to determine the role of the LTR and env gene in replication fitness and transmission efficiency. Replication fitness was assessed using a dual infection growth competition assay. We observed that primary HIV-1 subtype C isolates had higher overall relative fitness and transmission efficiency than primary subtype A isolates in PBMC and in an ex vivo cervical tissue derived organ culture, respectively. Furthermore, a comparison of replicative fitness between a subtype A/subtype C half genome chimeric virus and parental subtype A virus indicates that the higher replication fitness and transmission efficiency of subtype C virus over subtype A virus from India is not due to the env gene alone. We have also characterized the genetic structure and functional characteristics of subtype A and subtype C LTRs from India. Despite their apparent variability, no significant difference was observed in the transcriptional activity between the LTRs of subtype A and subtype C. Therefore, the LTR region alone is not responsible for higher replication fitness of subtype C over subtype A. The findings presented in this study are significant for public health because an understanding of the mechanism of the asymmetric distribution of HIV-1 subtypes in India is an important component in the development of strategies to control HIV-1 infection in this country.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Rodriguez, Milka Alejandramar4@pitt.edu; rodriguezmilka@hotmail.comMAR4
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAyyavoo, Velpandivelpandi@pitt.eduVELPANDI
Committee MemberGupta, Phalgunipgupta1@pitt.eduPGUPTA1
Committee MemberMontelaro, Ronaldrmont@pitt.eduRMONT
Committee MemberReinhart, Toddreinhar@pitt.eduREINHAR
Date: 27 September 2007
Date Type: Completion
Defense Date: 14 August 2007
Approval Date: 27 September 2007
Submission Date: 3 August 2007
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: India; HIV-1; replication fitness; subtype C
Other ID: http://etd.library.pitt.edu/ETD/available/etd-08032007-154959/, etd-08032007-154959
Date Deposited: 10 Nov 2011 19:56
Last Modified: 15 Nov 2016 13:48
URI: http://d-scholarship.pitt.edu/id/eprint/8858

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