Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors.
Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neurological manifestations both in adults and in children. The primary target for HIV-1 infection in the brain is the microglia, but astrocytes can also be infected. We tested 26 primary HIV-1 isolates for their capacity to infect human fetal astrocytes in culture. Eight of these isolates, independent of their biological phenotype and chemokine receptor usage, were able to infect astrocytes. Although no sustained viral replication could be demonstrated, the virus was recovered by coculture with receptive cells such as macrophages or on stimulation with interleukin-1beta. To gain knowledge into the molecular events that regulate attachment and penetration of HIV-1 in astrocytes, we investigated the expression of several chemokine receptors. Fluorocytometry and calcium-mobilization assay did not provide evidence of expression of any of the major HIV-1 coreceptors, including CXCR4, CCR5, CCR3, and CCR2b, as well as the CD4 molecule on the cell surface of human fetal astrocytes. However, mRNA transcripts for CXCR4, CCR5, Bonzo/STRL33/TYMSTR, and APJ were detected by RT-PCR. Furthermore, infection of astrocytes by HIV-1 isolates with different chemokine receptor usage was not inhibited by the chemokines SDF-1beta, RANTES, MIP-1beta, or MCP-1 or by antibodies directed against the third variable region or the CD4 binding site of gp120. These data show that astrocytes can be infected by primary HIV-1 isolates via a mechanism independent of CD4 or major chemokine receptors. Furthermore, astrocytes are potential carriers of latent HIV-1 and on activation may be implicated in spreading the infection to other neighbouring cells, such as microglia or macrophages.
Sabri
F
F
Microbiology and Tumorbiology Center, Karolinska Institute, Doktorsringen 13, Stockholm, 17177, Sweden.
Tresoldi
E
E
Di Stefano
M
M
Polo
S
S
Monaco
M C
MC
Verani
A
A
Fiore
J R
JR
Lusso
P
P
Major
E
E
Chiodi
F
F
Scarlatti
G
G
D000328:Adult; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000196:embryology; D015704:CD4 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002648:Child; D015870:Gene Expression; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007223:Infant; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism*; D014775:Virus Activation
D000911:Antibodies, Monoclonal; C515300:CCR1 protein, human; C515334:CCR2 protein, human; C515350:CCR3 protein, human; D015704:CD4 Antigens; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D019402:Macrophage Inflammatory Proteins; D010446:Peptide Fragments; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015728:Receptors, HIV