Colón Krystal, Vázquez-Santiago Fabián, Rivera-Amill Vanessa, Delgado Gisela, Massey Steven E, Wojna Valerie, Noel Richard J, Meléndez Loyda M
Department of Microbiology and Medical Zoology, University of Puerto Rico Medical Sciences Campus, San Juan, PR.
Department of Basic Sciences, Microbiology Division, Ponce Health Sciences University-School of Medicine, Ponce Research Institute, Ponce PR.
J Virol Antivir Res. 2015;4(3). doi: 10.4172/2324-8955.1000143. Epub 2015 Oct 6.
HIV-1 variants with different tropisms are associated with various neuropathologies. This study intends to determine if this correlation is determined by unique viral sequences. We hypothesize that HIV-1 envelope gene sequence changes are associated with cognition status.
Viral RNA was extracted from peripheral blood mononuclear cells (PBMCs) co-cultures derived from HIV-1 infected Hispanic women that had been characterized for HIV associated neurocognitive disorders (HAND).
Analyses of the C2V4 region of HIV gp120 demonstrated that increased sequence diversity correlates with cognition status as sequences derived from subjects with normal cognition exhibited less diversity than sequences derived from subjects with cognitive impairment. In addition, differences in V3 and V4 loop charges were also noted as well as differences in the N-glycosylation of the V4 region.
Our data suggest that the genetic signature within the C2V4 region may contribute to the pathogenesis of HAND. HIV sequence characteristics for the isolates grouped in milder forms of HAND can provide insightful information of prognostic value to assess neurocognitive status in HIV subjects, particularly during the era of highly prevalent milder forms of HAND.
具有不同嗜性的HIV-1变体与各种神经病理学相关。本研究旨在确定这种相关性是否由独特的病毒序列决定。我们假设HIV-1包膜基因序列变化与认知状态相关。
从感染HIV-1的西班牙裔女性的外周血单核细胞(PBMC)共培养物中提取病毒RNA,这些女性已被确定患有与HIV相关的神经认知障碍(HAND)。
对HIV gp120的C2V4区域的分析表明,序列多样性增加与认知状态相关,因为来自认知正常受试者的序列比来自认知受损受试者的序列表现出更少的多样性。此外,还注意到V3和V4环电荷的差异以及V4区域N-糖基化的差异。
我们的数据表明,C2V4区域内的基因特征可能有助于HAND的发病机制。分组为较轻形式HAND的分离株的HIV序列特征可为评估HIV受试者的神经认知状态提供具有预后价值的深刻见解信息,特别是在较轻形式HAND高度流行的时代。