Restriction of HIV type 1 infection in macrophages heterozygous for a deletion in the CC-chemokine receptor 5 gene

Lucia Ometto, Marisa Zanchetta, Anna Cabrelle, Giovanni Esposito, Monica Mainardi, Luigi Chieco-Bianchi, Anita De Rossi

Research output: Contribution to journalArticle

Abstract

Homozygosity for a 32-base pair deletion (Δ32) within the CC-chemokine receptor 5 (CCR5) gene confers resistance to infection by R5-type HIV-1 isolates. To ascertain how CCR5Δ32 heterozygosity influences the susceptibility of lymphocytes and macrophages to HIV-1 infection, peripheral blood lymphocytes (PBLs) and monocyte-derived macrophages (MDMs) from three HIV-1-uninfected CCR5Δ32 heterozygous infants and three HIV-1-uninfected CCR5 wild-type homozygous infants were exposed to two R5-type primary isolates. HIV-1 infection was monitored by DNA-PCR and p24 antigen determination; CCR5 and CCR5Δ32 transcripts were quantified by competitive reverse transcription-PCR. Wild-type homozygous MDMs and PBLs and heterozygous PBLs were infected by both viral isolates, albeit with different efficiencies, but heterozygous MDMs showed restriction to HIV-1 infection. Lower levels of CCR5 mRNA and protein expression were found in heterozygous versus wild-type homozygous MDMs and PBLs. Interestingly, wild-type homozygous MDMs showed higher levels of CCR5 mRNA expression compared with wild-type homozygous PBLs, while heterozygous MDMs had lower levels of CCR5 wild-type mRNA and a higher CCR5Δ32/CCR5 mRNA ratio compared with heterozygous PBLs. These findings suggest that CCR5Δ32 heterozygosity confers a different degree of protection against HIV-1 in PBLs and MDMs, depending on the ratio of wild-type and mutant CCR5 mRNA in the two cell types, and may delay virus spread in the host by preventing infection of monocytes and macrophages.

Original languageEnglish
Pages (from-to)1441-1452
Number of pages12
JournalAIDS Research and Human Retroviruses
Volume15
Issue number16
DOIs
Publication statusPublished - Nov 1 1999

ASJC Scopus subject areas

  • Immunology
  • Virology

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