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Titolo:
Restriction of HIV type 1 infection in macrophages heterozygous for a deletion in the CC-chemokine receptor 5 gene
Autore:
Ometto, L; Zanchetta, M; Cabrelle, A; Esposito, G; Mainardi, M; Chieco-Bianchi, L; De Rossi, A;
Indirizzi:
Univ Padua, Dept Oncol & Surg Sci, AIDS Ref Ctr, Oncol Sect, I-35128 Padua, Italy Univ Padua Padua Italy I-35128 Ref Ctr, Oncol Sect, I-35128 Padua, Italy
Titolo Testata:
AIDS RESEARCH AND HUMAN RETROVIRUSES
fascicolo: 16, volume: 15, anno: 1999,
pagine: 1441 - 1452
SICI:
0889-2229(19991101)15:16<1441:ROHT1I>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; VERTICAL TRANSMISSION; DISEASE PROGRESSION; UNINFECTED INDIVIDUALS; DELTA-CCR5 MUTATION; VIRAL PHENOTYPE; T-LYMPHOCYTES; SUSCEPTIBILITY; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: De Rossi, A Univ Padua, Dept Oncol & Surg Sci, AIDS Ref Ctr, Oncol Sect, I-35128 Padua, Italy Univ Padua Padua Italy I-35128 ol Sect, I-35128 Padua, Italy
Citazione:
L. Ometto et al., "Restriction of HIV type 1 infection in macrophages heterozygous for a deletion in the CC-chemokine receptor 5 gene", AIDS RES H, 15(16), 1999, pp. 1441-1452

Abstract

Homozygosity for a 32-base pair deletion (Delta 32) within the CC-chemokine receptor 5 (CCR5) gene confers resistance to infection by R5-type HIV-1 isolates. To ascertain how CCR5 Delta 32 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 CCR5 Delta 32 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 CCR5 Delta 32 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 CCR5 Delta 32/CCR5 mRNA ratio compared with heterozygous PBLs, These findings suggest that CCR5 Delta 32 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 06:20:15