Physical contact with lymphocytes is required for reactivation of dormant HIV-1 in colonic epithelial cells: involvement of the HIV-1 LTR.
HIV-1 transmission from mucosal epithelial cells to lymphocytes is a potential mechanism of HIV-1 contamination during sexual intercourse. The human colon epithelial cell line HT-29, that is infectable by various HIV-1 strains, is a useful model for studying the molecular mechanisms involved in this process. In the present study, we show that HT-29 cells, when exposed to either HIV-1(LAI) or HIV-1(NDK) at a low multiplicity of infection, became infected but did not produce infectious virions. Using two-compartment cell culture chambers separated by a porous membrane, we showed that PBL were able to rescue infectious HIV-1 from latently infected HT-29 cells following a physical interaction between the two cell populations. In contrast, HT-29 cells, infected with the same viruses at a high multiplicity of infection, were able to produce mature viral particles that were infectious to PBL in absence of cellular contacts. Transient expression assays using an indicator gene under the control of the HIV-1 long terminal repeat revealed that cell-to-cell contact induced an activation of the HIV-1 promoter. These observations provide a putative molecular mechanism for transmission of HIV-1 from mucosal epithelial cells to lymphocytes.
Institut de Chimie Biologique, Université de Provence, Marseille, France.
E
E
Faure
N
N
Yahi
A
A
Zider
C
C
Cavard
S
S
Champion
J
J
Fantini
D002450:Cell Communication; D002460:Cell Line; D002461:Cell Line, Transformed; D003106:Colon / Q000166:cytology / Q000821:virology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D002523:Edible Grain / Q000166:cytology; D004847:Epithelial Cells; D004848:Epithelium / Q000821:virology; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D005813:Genes, Synthetic; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000821:virology*; D008222:Lymphokines / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology*; D014775:Virus Activation; D014779:Virus Replication
D017077:Culture Media, Conditioned; D008222:Lymphokines