1. Viral characteristics associated with maintenance of elite neutralizing activity in chronically HIV-1 clade C infected monozygotic pediatric twins.
- Author
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Mishra, Nitesh, Makhdoomi, Muzamil Ashraf, Sharma, Shaifali, Kumar, Sanjeev, Dobhal, Ayushman, Kumar, Deepshikha, Chawla, Himanshi, Singh, Ravinder, Kanga, Uma, Das, Bimal Kumar, Lodha, Rakesh, Kabra, Sushil K., and Luthra, Kalpana
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TWINS , *IMMUNOGLOBULINS , *VIRAL antibodies , *OVERTIME , *VIRUSES - Abstract
Broad and potent neutralizing antibodies (bnAbs) with multiple epitope specificities evolve in HIV-1 infected children. Herein, we studied two antiretroviral naïve chronically HIV-1C in fected monozygotic pediatric twins AIIMS_329 and AIIMS_330 with potent plasma bnAbs. Elite plasma neutralizing activity was observed since initial sampling at 78 months in AIIMS_330 and persisted throughout, while in AIIMS_329 it was seen at 90-months of age after which potency decreased overtime. We evaluated potential viral characteristics associat ed with varied immune profile by generating single genome amplified pseudoviruses. The AIIMS_329 viruses generated from 90-month time point were neutralization sensitive to bnAbs and contemporaneous plasma antibodies, while viruses from 112-month and 117-month timepoints were resistant to most bnAbs and contemporaneous plasma. AIIMS_329 viruses developed resistance to plasma nAbs plausibly by N160-glycan loss, V1- and V4- loop lengthening. The viruses generated from AIIMS_330 (at 90 and 117-months) showed varied susceptibility to bnAbs and autologous contemporaneous plasma antibodies while the viruses of 112-month timepoint, at which plasma nAb specificities mapped to the V2-glycan, V3-glycan and CD4bs, were resistant to contemporaneous plasma antibodies as well as to most bnAbs. Chimeric viruses were constructed from 90-month time-point PG9 sensitive AIIMS-329 and AIIMS_330 viruses with swapped V1V2 regions of their respective evolved viruses (at 112 and 117-month), that led to higher resistance to neutralization by PG9 and autologous plasma antibodies. We observed evolution of a viral pool in AIIMS_330 donor, comprising of plasma antibody neutralization sensitive or resistant diverse autologous viruses that may have contributed to development and maintenance of elite neutralizing activity. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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