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(Unpublished)
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Unpublished |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: |
|
| ETD Committee: |
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| 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: |
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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