OBJECTIVES: To examine the relationship between the humoral immune response and viral envelope diversity among HIV/AIDS patients with or without HIV-associated dementia (HAD). METHODS: Whole blood and sera were collected from age- and disease-progression matched AIDS-defined patients with and without neuro-cognitive impairment at two centers. Peripheral blood mononuclear cells were isolated from whole blood and separated into monocyte/macrophage and peripheral blood lymphocyte (PBL) preparations. Genomic DNA, isolated from the PBL population, was used as template to amplify HIV-1 C2V3 envelope sequences in a nested PCR protocol. The resulting fragments were sequenced and subjected to a phylogenetic analysis. RESULTS: Sera from non-demented (ND; n = 21) patients neutralized infection of CCR5-dependent, but not CXCR4-dependent viruses, more efficiently than sera from HAD patients (n = 15) (P < 0.05). A recombinant virus containing a brain derived C2V3 sequence was also neutralized less efficiently by sera from HAD patients ( < 0.05). C2V3 envelope sequences amplified from PBL revealed significantly greater diversity within the V3 region from HAD compared with ND patients (P < 0.001). The number of non-synonymous substitutions was positively correlated with the severity of neuro-cognitive impairment of patients (P < 0.005). Similarly, brain derived V3 sequences exhibited significantly increased diversity among HAD patients (P < 0.001). CONCLUSION: Our findings imply that HAD patients exhibited impaired serological responses that may lead to the emergence of viral mutants that potentially could infect the brain and mediate neurodegeneration.
OBJECTIVES: To examine the relationship between the humoral immune response and viral envelope diversity among HIV/AIDSpatients with or without HIV-associated dementia (HAD). METHODS: Whole blood and sera were collected from age- and disease-progression matched AIDS-defined patients with and without neuro-cognitive impairment at two centers. Peripheral blood mononuclear cells were isolated from whole blood and separated into monocyte/macrophage and peripheral blood lymphocyte (PBL) preparations. Genomic DNA, isolated from the PBL population, was used as template to amplify HIV-1 C2V3 envelope sequences in a nested PCR protocol. The resulting fragments were sequenced and subjected to a phylogenetic analysis. RESULTS: Sera from non-demented (ND; n = 21) patients neutralized infection of CCR5-dependent, but not CXCR4-dependent viruses, more efficiently than sera from HADpatients (n = 15) (P < 0.05). A recombinant virus containing a brain derived C2V3 sequence was also neutralized less efficiently by sera from HADpatients ( < 0.05). C2V3 envelope sequences amplified from PBL revealed significantly greater diversity within the V3 region from HAD compared with NDpatients (P < 0.001). The number of non-synonymous substitutions was positively correlated with the severity of neuro-cognitive impairment of patients (P < 0.005). Similarly, brain derived V3 sequences exhibited significantly increased diversity among HADpatients (P < 0.001). CONCLUSION: Our findings imply that HADpatients exhibited impaired serological responses that may lead to the emergence of viral mutants that potentially could infect the brain and mediate neurodegeneration.
Authors: Guido van Marle; Deirdre L Church; Kali D Nunweiler; Kris Cannon; Mark A Wainberg; M John Gill Journal: Retrovirology Date: 2010-09-13 Impact factor: 4.602
Authors: Maria J Polyak; Pornpun Vivithanaporn; Ferdinand G Maingat; John G Walsh; William Branton; Eric A Cohen; Rick Meeker; Christopher Power Journal: FASEB J Date: 2013-04-22 Impact factor: 5.191
Authors: Rebecca L Dunfee; Elaine R Thomas; Jianbin Wang; Kevin Kunstman; Steven M Wolinsky; Dana Gabuzda Journal: Virology Date: 2007-06-27 Impact factor: 3.616