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HIV migration between blood plasma and cellular subsets before and after HIV therapy

 Jun Yong Choi  ;  Antoine Chai llon  ;  Jin Ok Oh  ;  Jin Young Ahn  ;  Hae Won Ann  ;  In Young Jung  ;  Mi-Young Ahn  ;  Yong Duk Jeon  ;  Nam Su Ku  ;  Davey M. Smith  ;  June Myung Kim 
 JOURNAL OF MEDICAL VIROLOGY, Vol.88(4) : 606-613, 2016 
Journal Title
Issue Date
Adult ; Anti-Retroviral Agents/therapeutic use ; DNA, Viral/chemistry ; DNA, Viral/genetics ; HIV Infections/drug therapy ; HIV Infections/virology* ; HIV-1/classification ; HIV-1/genetics ; HIV-1/isolation & purification* ; Humans ; Leukocytes, Mononuclear/virology* ; Male ; Middle Aged ; Plasma/virology* ; RNA, Viral/blood* ; RNA, Viral/genetics ; Sequence Analysis, DNA ; env Gene Products, Human Immunodeficiency Virus/genetics
HIV ; antiretroviral therapy ; cladistics analysis ; compartmentalization ; reservoir ; viremia
The cellular source of HIV RNA circulating in blood plasma remains unclear. Here, we investigated whether sequence analysis of HIV RNA populations circulating before combination antiretroviral therapy (cART) and HIV DNA populations in cellular subsets (CS) after cART could identify the cellular sources of circulating HIV RNA. Blood was collected from five subjects at cART initiation and again 6 months later. Naïve CD4+ T cells, resting central memory and effector memory CD4+ T cells, activated CD4+ T cells, monocytes, and natural killer cells were sorted using a fluorescence-activated cell sorter. HIV-1 env C2V3 sequences from HIV RNA in blood plasma and HIV DNA in CSs were generated using single genome sequencing. Sequences were evaluated for viral compartmentalization (Fst test) and migration events (MEs; Slatkin Maddison and cladistic measures) between blood plasma and each CS. Viral compartmentalization was observed in 88% of all cellular subset comparisons (range: 77-100% for each subject). Most observed MEs were directed from blood plasma to CSs (52 MEs, 85.2%). In particular, there was only viral movement from plasma to NK cells (15 MEs), monocytes (seven MEs), and naïve cells (five ME). We observed a total of nine MEs from activated CD4 cells (2/9 MEs), central memory T cells (3/9 MEs), and effector memory T cells (4/9 MEs) to blood plasma. Our results revealed that the HIV RNA population in blood plasma plays an important role in seeding various cellular reservoirs and that the cellular source of the HIV RNA population is activated central memory and effector memory T cells.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Ku, Nam Su(구남수) ORCID logo https://orcid.org/0000-0002-9717-4327
Kim, June Myung(김준명)
Ahn, Mi Young(안미영)
Ahn, Jin Young(안진영) ORCID logo https://orcid.org/0000-0002-3740-2826
Jeon, Yong Duk(전용덕)
Jung, In Young(정인영)
Choi, Jun Yong(최준용) ORCID logo https://orcid.org/0000-0002-2775-3315
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