HIV migration between blood plasma and cellular subsets before and after HIV therapy.
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.
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.|AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Jun Yong
JY
Choi
Department of Medicine, University of California San Diego, La Jolla, California.|Veterans Affairs San Diego Healthcare System, San Diego, California.
Antoine
A
Chaillon
AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Jin Ok
JO
Oh
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.|AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Jin Young
JY
Ahn
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.|AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Hae Won
HW
Ann
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
In Young
IY
Jung
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Mi-Young
MY
Ahn
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Yong Duk
YD
Jeon
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.|AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Nam Su
NS
Ku
Department of Medicine, University of California San Diego, La Jolla, California.|Veterans Affairs San Diego Healthcare System, San Diego, California.
Davey M
DM
Smith
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.|AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
June Myung
JM
Kim
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology*; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D017422:Sequence Analysis, DNA; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus
HIV; antiretroviral therapy; cladistics analysis; compartmentalization; reservoir; viremia