scholarly journals Longitudinal Analysis of Human Immunodeficiency Virus Type 1 nef/Long Terminal Repeat Sequences in a Cohort of Long-Term Survivors Infected from a Single Source

2006 ◽  
Vol 80 (2) ◽  
pp. 1047-1052 ◽  
Author(s):  
Melissa J. Churchill ◽  
David I. Rhodes ◽  
Jennifer C. Learmont ◽  
John S. Sullivan ◽  
Steven L. Wesselingh ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Long Terminal Repeat ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Single Source ◽  
Immunodeficiency Virus ◽  
Long Term Survivors ◽  
Hiv 1

ABSTRACT We studied the evolution of human immunodeficiency virus type 1 (HIV-1) in a cohort of long-term survivors infected with an attenuated strain of HIV-1 acquired from a single source. Although the cohort members experienced differing clinical courses, we demonstrate similar evolution of HIV-1 nef/long-terminal repeat (LTR) sequences, characterized by progressive sequence deletions tending toward a minimal nef/LTR structure that retains only sequence elements required for viral replication. The in vivo pathogenicity of attenuated HIV-1 is therefore dictated by viral and/or host factors other than those that impose a unidirectional selection pressure on the nef/LTR region of the HIV-1 genome.

scholarly journals Characterization of Three nef-Defective Human Immunodeficiency Virus Type 1 Strains Associated with Long-Term Nonprogression

2000 ◽  
Vol 74 (22) ◽  
pp. 10581-10588 ◽  
Author(s):  
David I. Rhodes ◽  
Lesley Ashton ◽  
Ajantha Solomon ◽  
Andrew Carr ◽  
David Cooper ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Mononuclear Cells ◽  
Pathogenic Potential ◽  
Immunodeficiency Virus ◽  
Long Term Survivors ◽  
Hiv 1

ABSTRACT Long-term survivors (LTS) of human immunodeficiency virus type 1 (HIV-1) infection provide an opportunity to investigate both viral and host factors that influence the rate of disease progression. We have identified three HIV-1-infected individuals in Australia who have been infected for over 11 years with viruses that contain deletions in the nef and nef-long terminal repeat (nef/LTR) overlap regions. These viruses differ from each other and from other nef-defective strains of HIV-1 previously identified in Australia. One individual, LTS 3, is infected with a virus containing a nef gene with a deletion of 29 bp from the nef/LTR overlap region, resulting in a truncated Nef open reading frame. In addition to the Nef defect, only viruses containing truncated Vif open reading frames of 37 or 69 amino acids could be detected in peripheral blood mononuclear cells isolated from this patient. LTS 3 had a viral load of less than 20 copies of RNA/ml of plasma. The other two long-term survivors, LTS 9 and LTS 11, had loads of less than 200 copies of RNA/ml of plasma and are infected with viruses with larger deletions in both thenef alone and nef/LTR overlap regions. These viruses contain wild-type vif, vpu, andvpr accessory genes. All three strains of virus had envelope sequences characteristic of macrophagetropic viruses. These findings further indicate the reduced pathogenic potential ofnef-defective viruses.

scholarly journals Effective Suppression of Human Immunodeficiency Virus Type 1 through a Combination of Short- or Long-Hairpin RNAs Targeting Essential Sequences for Retroviral Integration

2006 ◽  
Vol 80 (15) ◽  
pp. 7658-7666 ◽  
Author(s):  
Hironori Nishitsuji ◽  
Michinori Kohara ◽  
Mari Kannagi ◽  
Takao Masuda
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Attachment Site ◽  
High Dose ◽  
Wild Type ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Small interfering RNA (siRNA) could provide a new therapeutic approach to treating human immunodeficiency virus type 1 (HIV-1) infection. For long-term suppression of HIV-1, emergence of siRNA escape variants must be controlled. Here, we constructed lentiviral vectors encoding short-hairpin RNAs (shRNA) corresponding to conserved target sequences within the integrase (int) and the attachment site (att) genes, both of which are essential for HIV-1 integration. Compared to shRNA targeting of the HIV-1 transcription factor tat (shTat), shRNA against int (shIN) or the U3 region of att (shU3) showed a more potent inhibitory effect on HIV-1 replication in human CD4+ T cells. Infection with a high dose of HIV-1 resulted in the emergence of escape mutants during long-term culture. Of note, limited genetic variation was observed in the viruses resistant to shIN. A combination of shINs against wild-type and escape mutant sequences had a negative effect on their antiviral activities, indicating a potentially detrimental effect when administering multiple shRNA targeting the same region to combat HIV-1 variants. The combination of shIN and shU3 att exhibited the strongest anti-HIV-1 activity, as seen by complete abrogation of viral DNA synthesis and viral integration. In addition, a modified long-hairpin RNA spanning the 50 nucleotides in the shIN target region effectively suppressed wild-type and shIN-resistant mutant HIV-1. These results suggest that targeting of incoming viral RNA before proviral DNA formation occurs through the use of nonoverlapping multiple siRNAs is a potent approach to achieving sustained, efficient suppression of highly mutable viruses, such as HIV-1.

scholarly journals Dynamics of Human Immunodeficiency Virus Type 1 Replication in Vertically Infected Infants

1999 ◽  
Vol 73 (1) ◽  
pp. 362-367 ◽  
Author(s):  
Katherine Luzuriaga ◽  
Hulin Wu ◽  
Margaret McManus ◽  
Paula Britto ◽  
William Borkowsky ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Drug Regimen ◽  
Turnover Rates ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Plasma human immunodeficiency virus type 1 (HIV-1) turnover and kinetics were studied in children aged 15 days to 2 years following the initiation of a triple antiretroviral drug regimen consisting of zidovudine, lamivudine, and nevirapine. HIV-1 turnover was at least as rapid as that previously described in adults; turnover rates were more rapid in infants and children aged 3 months to 2 years than in infants less than 3 months of age. These data confirm the central role of HIV-1 replication in the pathogenesis of vertical HIV-1 infection and reinforce the importance of early, potent combination therapies for the long-term control of HIV-1 replication.

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