Different hypotheses have been postulated to explain the naturally long but variable progression of HIV-1 infection. An understanding of the reasons for this variable pattern of disease progression is of fundamental importance in AIDS research. Based on the most recent evidence, a new fundamental theory is considered prevalent. This theory proposes that the proven shift in tropism HIV-1 infection soon becomes deadly because T-lymphocyte tropic viruses (T-tropic, X4) replicate at a much higher rate and kill more cells than the macrophage-tropic viruses (M-tropic, RS) consistently seen in initial infection. This theory, although popular and prevalent, is not yet a proven hypothesis of how HIV becomes increasingly cytotoxic and thereby influences disease progression. We hypothesize that the early appearance of T-tropic virus in patient plasma will precede or directly relate to fast progression. We also believe that the CD-4 T-lymphocyte sub-population depletion patterns will relate to or even predict the appearance of T-tropic viral variants. Therefore, we propose to document and better characterize the viral variants, genomic and tropic involved in different rates of progression in Puerto Rican patients and their T-lymphocyte sub-population depletion patterns. We will compare approximately twenty fast progressors with twenty normal/slow progressors. We propose to do a study, sub-cloning and sequencing the C2V3 region of the envelope gene, at multiple time points, from all patients in both cohorts. We will track viral evolution and diversity by studying the tendency to form clusters associated with sampling time in the phylogenetic re-constructions. A consensus motif in the V3 domain that predicts CCR5 usage (M-tropic/R5) has been delineated. Based on this consensus, we propose to identify the tropism of the viral forms present at these sampling time points by genomic sequence analyses of the V3 envelope region, in order to better understand tropism and disease progression. We also propose to conduct a flow-cytometry study of both cohorts at these sampling time points to evaluate if the recent discovery (1999) of the """"""""ex-vivo"""""""" depletion of a CD4-CCR5 T-lymphocyte sub-population caused by M-tropic virus relates to or precedes the eventual appearance in plasma of T-tropic viruses. This may provide an early, efficient and cost effective marker of disease progression.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
2S06GM008239-16
Application #
6325551
Study Section
Minority Programs Review Committee (MPRC)
Project Start
1986-09-30
Project End
2005-05-31
Budget Start
Budget End
Support Year
16
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Ponce School of Medicine
Department
Type
DUNS #
City
Ponce
State
PR
Country
United States
Zip Code
00732
Diaz-Zabala, Hector J; Ortiz, Ana P; Garland, Lisa et al. (2018) A Recurrent BRCA2 Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico. Cancers (Basel) 10:
Cuevas, Marielly; Cruz, Myrella L; Ramirez, Antonio E et al. (2018) Stress During Development of Experimental Endometriosis Influences Nerve Growth and Disease Progression. Reprod Sci 25:347-357
Encarnación, Jarline; Ortiz, Carmen; Vergne, Ralphdy et al. (2016) High DRC Levels Are Associated with Let-7b Overexpression in Women with Breast Cancer. Int J Mol Sci 17:
Matta, Jaime; Morales, Luisa; Ortiz, Carmen et al. (2016) Estrogen Receptor Expression Is Associated with DNA Repair Capacity in Breast Cancer. PLoS One 11:e0152422
Ruiz, Lynnette A; Báez-Vega, Perla M; Ruiz, Abigail et al. (2015) Dysregulation of Lysyl Oxidase Expression in Lesions and Endometrium of Women With Endometriosis. Reprod Sci 22:1496-508
Quiñones, Maria; Urrutia, Rebecca; Torres-Reverón, Annelyn et al. (2015) Anxiety, coping skills and hypothalamus-pituitary-adrenal (HPA) axis in patients with endometriosis. J Reprod Biol Health 3:
Pérez, Wanda I; Soto, Yarelys; Ortíz, Carmen et al. (2015) Ferrocenes as potential chemotherapeutic drugs: synthesis, cytotoxic activity, reactive oxygen species production and micronucleus assay. Bioorg Med Chem 23:471-9
Mateo, Z; Porter, J T (2015) Developmental decline in modulation of glutamatergic synapses in layer IV of the barrel cortex by group II metabotropic glutamate receptors. Neuroscience 290:41-8
Fourquet, Jessica; Sinaii, Ninet; Stratton, Pamela et al. (2015) Characteristics of women with endometriosis from the USA and Puerto Rico. J Endometr Pelvic Pain Disord 7:129-135
Matos-Ocasio, Félix; Hernández-López, Anixa; Thompson, Kenira J (2014) Ceftriaxone, a GLT-1 transporter activator, disrupts hippocampal learning in rats. Pharmacol Biochem Behav 122:118-21

Showing the most recent 10 out of 91 publications