HIV-1 infection of trophoblasts is independent of gp120/CD4 Interactions but relies on heparan sulfate proteoglycans.
Mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) is the leading cause of HIV infection in infants. Direct infection of trophoblasts--cells forming the placental barrier--may cause this transmission. Entry of HIV-1 into trophoblasts is unusual for this retrovirus, because it is associated with endocytosis. However, given that trophoblasts express no or few receptors/coreceptors required for virus internalization, the mechanism underlying this event remains ambiguous. In the present study, we show that HIV-1 entry and infection of polarized trophoblasts are independent not only of CD4 but also of envelope (Env) glycoproteins gp120 and gp41. Virus internalization, cytoplasmic release, reverse transcription, integration, and HIV-1 gene expression occurred with both fusion-incompetent and Env-deficient viruses. Importantly, fusion-independent infection was observed when we used viruses produced in a natural cellular reservoir (i.e., primary human cells). Finally, HIV-1 requires heparan sulfate proteoglycans for uptake in trophoblasts. Together, our findings illustrate that HIV-1 utilizes an unusual pathway for entering human polarized trophoblasts.
Vidricaire
Gael
G
Research Center in Infectious Diseases, Centre Hospitalier de l'Universite Laval Research Center, Laval University, Quebec, G1V 4G2, Canada.
Gauthier
Sonia
S
Tremblay
Michel J
MJ
D000163:Acquired Immunodeficiency Syndrome / Q000635:transmission*; D019013:CD40 Antigens / Q000502:physiology*; D002460:Cell Line; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015700:HIV Envelope Protein gp41 / Q000502:physiology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D019169:Jurkat Cells; D014327:Trophoblasts / Q000821:virology*
D019013:CD40 Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D019812:Heparan Sulfate Proteoglycans