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Different Pathogenesis of CCR5-Using Primary HIV-1 Isolates from Non-Switch and Switch Virus Patients in Human Lymphoid Tissue Ex VivoCCR5-utilizing HIV-1 variants (R5) typically transmit infection and dominate its early stages, whereas emergence of CXCR4-using (X4 or R5X4) HIV-1 is often associated with disease progression. However, such a switch in co-receptor usage can only be detected in approximately onehalf of HIV-infected patients (switch virus patients), and progression to immunodeficiency may also occur in patients without detectable switch in co-receptor usage (non-switch virus patients). Here, we used a system of ex vivo-infected tonsillar tissue to compare the pathogenesis of sequential primary R5 HIV-1 isolates from the switch and non-switch patients. Inoculation of ex vivo tissue with these R5 isolates resulted in viral replication and CCR5(+)CD4(+) T cell depletion. The levels of such depletion by HIV-1 isolated from non-switch virus patients were significantly higher than those by R5 HIV-1 isolates from switch virus patients. T cell depletion seemed to be controlled by viral factors and did not significantly vary between tissues from different donors. In contrast, viral replication did not correlate with the switch status of the patients; in tissues fiom different donors it varied 30-fold and seemed to be controlled by a combination of viral and tissue factors. Nevertheless, replication-level hierarchy among sequential isolates remained constant in tissues from various donors. Viral load in vivo was higher in switch virus patients compared to non-switch virus patients. The high cytopathogenicity of CCR5(+)CD4(+) T cells by R5 HIV-1 isolates from non-switch virus patients may explain the steady decline of CD4(+) T cells in the absence of CXCR4 using virus; elimination of target cells by these isolates may limit their own replication in vivo.
Document ID
20060055231
Acquisition Source
Johnson Space Center
Document Type
Conference Paper
Authors
Iarlsson, Ingrid
(Lund Univ. Sweden)
Grivel, Jean-Charles
(Wyle Labs., Inc. Houston, TX, United States)
Chen. Silvia
(Wyle Labs., Inc. Houston, TX, United States)
Karlsson, Anders
(Venhalsan Stockholm, Sweden)
Albert, Jan
(Karolinska Inst. Stockholm, Sweden)
Fenyol, Eva Maria
(National Inst. of Health Bethesda, MD, United States)
Margolis, Leonid B.
(National Inst. of Health Bethesda, MD, United States)
Date Acquired
August 23, 2013
Publication Date
January 10, 2005
Subject Category
Life Sciences (General)
Report/Patent Number
W05-002
Funding Number(s)
CONTRACT_GRANT: NAS9-02078
Distribution Limits
Public
Copyright
Work of the US Gov. Public Use Permitted.

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