New T-lymphocytic cell lines for studying cell infectability by human immunodeficiency virus.
We identified five human T-lymphoid cell lines (PB-1, Sez-4, C19PL, HUT 102B and ATL-2) which highly express CD4 in addition to CXCR4 and CCR5. In order to evaluate if these cells are infectabile by human immunodeficiency virus (HIV) and could be employed as a model in HIV research we exposed these cell lines to X4 (T-cell tropic) and R5 (macrophage tropic) and subsequently tried to correlate their infectability with (i) level of chemokine coreceptor (CXCR4 and CCR5) expression, (ii) coreceptor functionality (calcium flux, chemotaxis and phosphorylation of MAPK p42/44 and AKT) and (iii) endogenous expression and secretion of HIV-related chemokines which compete with the virus for binding to CXCR4 (SDF-1/CXCL12) or CCR5 (MIP-1beta/CCL4, MIP-1alpha/CCL3, RANTES/CCL5, MCP-2/CCL8, MCP-3/CCL7 and MCP-4/CCL13). We demonstrated that while PB-1 cells are infectable by both X4 and R5 HIV, Sez-4, C91PL, HUT 102B and ATL-2 cells were infected by X4 HIV only. Moreover, we noticed that the susceptibility of these cells to HIV did not correspond either with the level of surface expression or with the functionality of CXCR4 or CCR5; however, it was modulated to some degree by the endogenously secreted HIV-related chemokines. Thus all five mature T-cell lines described here may provide useful new models for studying various aspects of HIV infection. In addition we demonstrate that the infectability of cells by HIV is modulated by so far unidentified intrinsic factors as well as some already known endogenously secreted chemokines. The identification of these factors may be important for developing new strategies to protect cells from HIV infection.
Rozmyslowicz
T
T
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Kijowski
J
J
Conover
D O
DO
Majka
M
M
Baj-Krzyworzeka
M
M
Reca
R
R
Libura
J J
JJ
Gaulton
G N
GN
Ratajczak
M Z
MZ
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002633:Chemotaxis / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology / Q000473:pathology; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D015728:Receptors, HIV / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D014779:Virus Replication / Q000276:immunology
D015728:Receptors, HIV; D002118:Calcium