Human immunodeficiency virus type 1 bound to B cells: relationship to virus replicating in CD4+ T cells and circulating in plasma.
Human immunodeficiency virus type 1 (HIV-1) virions bind to B cells in the peripheral blood and lymph nodes through interactions between CD21 on B cells and complement-complexed virions. B-cell-bound virions have been shown to be highly infectious, suggesting a unique mode of HIV-1 dissemination by B cells circulating between peripheral blood and lymphoid tissues. In order to investigate the relationship between B-cell-bound HIV-1 and viruses found in CD4+ T cells and in plasma, we examined the genetic relationships of HIV-1 found in the blood and lymph nodes of chronically infected patients with heteroduplex mobility and tracking assays and DNA sequence analysis. In samples from 13 of 15 patients examined, HIV-1 variants in peripheral blood-derived B cells were closely related to virus in CD4+ T cells and more divergent from virus in plasma. In samples from five chronically viremic patients for whom analyses were extended to include lymph node-derived HIV-1 isolates, B-cell-associated HIV-1 and CD4+-T-cell-associated HIV-1 in the lymph nodes were equivalent in their divergence from virus in peripheral blood-derived B cells and generally more distantly related to virus in peripheral blood-derived CD4+ T cells. These results indicates virologic cross talk between B cells and CD4+ T cells within the microenvironment of lymphoid tissues and, to a lesser extent, between cells in lymph nodes and the peripheral blood. These findings also indicate that most of the virus in plasma originates from cells other than CD4(+) T cells in the peripheral blood and lymph nodes.
Malaspina
Angela
A
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Moir
Susan
S
Nickle
David C
DC
Donoghue
Eileen T
ET
Ogwaro
Kisani M
KM
Ehler
Linda A
LA
Liu
Shuying
S
Mican
Jo Ann M
JA
Dybul
Mark
M
Chun
Tae-Wook
TW
Mullins
James I
JI
Fauci
Anthony S
AS
D001402:B-Lymphocytes / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics*; D020180:Heteroduplex Analysis; D006801:Humans; D008198:Lymph Nodes / Q000821:virology; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D017422:Sequence Analysis, DNA; D014779:Virus Replication
D012367:RNA, Viral