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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-08032007-154959 |
| Date | 27 September 2007 |
| Creators | Rodriguez, Milka Alejandra |
| Contributors | Todd Reinhart, Velpandi Ayyavoo, Phalguni Gupta, Ronald Montelaro |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-08032007-154959/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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