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Current
HIV Research
ISSN: 1570-162X
Upcoming Articles
Levels of N-linked Glycosylation on the
V1 Loop of HIV-1 Env Proteins and their Relationship to the
Antigenicity of Env from Primary Viral Isolates
Zuhu Huanga, Arthur Chou,
Jonathan Tanguay, Siyuan Shen, Innocent
Mboudjeka, Te-Hui Chou, Shan Lu
and Shixia Wang
[Abstract]
HIV-1-Specific Cytotoxic T Lymphocyte (CTL) Responses
Against Immunodominant Optimal Epitopes Slow the Progression
of AIDS in China
Song Zhai,
Yan Zhuang, Yang Song,
Shu Li, Dedong Huang,
Wenzhen Kang, Xinhong Li,
Qi Liao, Yanhou Liu,
Zhongfang Zhao, Yichen Lu and Yongtao Sun
[Abstract]
Evaluation of HIV-1 and CD4+ T Cell Dynamic Parameters
in Patients Treated with Genotypic Resistance Testing-Guided
HAART
A. Cappuccio, F.
Castiglione1, B. Piccoli,
V. Tozzi
[Abstract]
Cessation of HIV-1 Transcription by Inhibiting Regulatory
Protein Rev Mediated RNA Transport
Yuan Cao, Xinyong
Liu and Erik De Clercq
[Abstract]
Rosuvastatin, Pravastatin, and Atorvastatin for the Treatment
of Hypercholesterolaemia in HIV-Infected Patients Receiving
Protease Inhibitors
Leonardo Calza,
Roberto Manfredi, Vincenzo
Colangeli, Daria Pocaterra, Michele Pavoni and Francesco Chiodo
[Abstract]
Abstracts
[Back to top]
Levels of N-linked Glycosylation on the V1 Loop
of HIV-1 Env Proteins and their Relationship to the Antigenicity
of Env from Primary Viral Isolates
Zuhu Huanga, Arthur Chou,
Jonathan Tanguay, Siyuan Shen, Innocent
Mboudjeka, Te-Hui Chou, Shan Lu
and Shixia Wang
A good understanding about the structure and function
of the envelope glycoprotein (Env) from primary human immunodeficiency
virus-1 (HIV-1) isolates is important in facilitating the
development of effective neutralizing antibody responses as
a component of an effective HIV-1 vaccine. In the current
study, the antigenicity of a panel of diverse HIV-1 primary
Env from different clades of HIV-1 Group M was analyzed using
rabbit sera produced by either 3- or 9-valent gp120 DNA vaccine
formulations. Both the 3- and 9-valent gp120 DNA vaccine formulations
elicited HIV-1 gp120-specific antibodies in immunized rabbits.
However, we observed two levels of primary envelope antigenicity
to the same set of rabbit immune sera and that the level of
glycosylation, particularly in the V1 loop, may contribute
to such diversity. Bioinformatics analysis on the distribution
and average number of the N-linked glycosylation sites in
all variable regions (V1–V5) was conducted. A linear
plot demonstrated that the average number of potential N-glycosylation
sites in the V1 and V4 loops correlates to the size of the
loop. These data provide further evidence on the complexity
of primary HIV-1 Env antigens and offers new insight into
the mechanisms that HIV-1 uses to escape protective immune
responses.
[Back to top]
HIV-1-Specific Cytotoxic T Lymphocyte (CTL) Responses
Against Immunodominant Optimal Epitopes Slow the Progression
of AIDS in China
Song Zhai,
Yan Zhuang, Yang Song,
Shu Li, Dedong Huang,
Wenzhen Kang, Xinhong Li,
Qi Liao, Yanhou Liu,
Zhongfang Zhao, Yichen Lu and Yongtao Sun
To assess the immunodominance patterns of HIV-1-specific cytotoxic
T lymphocyte (CTL) responses and the contribution of these
responses against the peptides scanning optimal epitopes in
chronic infection, we test the HIV-1-specific CTL responses
against a panel of 413 overlapping peptides spanning HIV-1
Asian B sequence, including 147 peptides corresponding to
optimal clade B epitopes in 49 chronically HIV-1 infected
individuals by interferon-γ
Elispot assay. A large variation in the recognition
of peptides restricted by the same HLA class I allele is presented.
Some epitopes are targeted frequently by individuals while
other epitopes restricted by the same allele are rarely recognized
in our research. HLA-B35 and HLA-A03 rather than other HLA
alleles contribute greatly to total virus-specific CTL responses.
Furthermore, there is a significant inverse correlation between
the total contribution of HIV-1-specific CTL responses restricted
by different HLA alleles to virus-specific immune responses
and viral load in the individuals during advanced infection
(P=0.002, r=-0.549). The peptides targeted by individuals
have significantly lower entropy compared with those not targeted
but restricted by the same HLA class I alleles (P<0.05)
in 49 individuals infected by HIV-1, especially the advanced
infection subgroup (P=0.044). These data demonstrate
that the consistent immunodominance patterns of HIV-1-specific
CTL responses of Chinese HIV-1 infected individuals and an
inverse correlation between the relative contribution of responses
restricted by HLA alleles and viral load, which indicates
the important protective effect of optimal epitopes against
slow disease progression even in advanced infection.
[Back to top]
Evaluation of HIV-1 and CD4 T Cell
Dynamic Parameters in Patients Treated with Genotypic Resistance
Testing-Guided HAART
A. Cappuccio, F. Castiglione, B. Piccoli,
V. Tozzi
The extent of immune restoration in HIV-1 patients on
antiretroviral therapy is an important marker of disease progression.
In this work, we investigate the dynamics of immune reconstitution
and address the question of whether the early response to
antiretroviral treatments allows to predict the late immune
restoration.
We select a cohort of twelve patients on GRT-HAART who achieve
virological suppression, but show variable recovery of immune
competence. HIV-RNA and CD4+ T cell assessments
are used for estimation of the dynamic parameters of an established
mathematical model of the viral-immune system interactions.
We find that failure in immune reconstitution is associated
with an abnormal increase of the death rate of uninfected
CD4+ T cells. In contrast, their production rate
is up to three times higher than in healthy seronegative individuals.
This finding is in line with the view of chronic activation
as a major cause of immune depletion. According to non parametric
statistics, CD4+ T cell responders and non responders
do not show significantly different dynamic parameters. Such
result suggests that the employed model does not allow to
predict the long term immune reconstitution.
[Back to top]
Cessation of HIV-1 Transcription by Inhibiting Regulatory
Protein Rev Mediated RNA Transport
Yuan Cao, Xinyong
Liu and Erik De Clercq
The HIV-1 Rev protein, which traffics through nucleolus and
shuttles between nucleus and cytoplasm, facilitates export
of unspliced and singly spliced viral transcripts containing
RRE RNA by the CRM1 export pathway. Inhibitions of the various
stages of Rev-mediated RNA transport can arrest HIV-1 transcriptional
process. The current understanding to the mechanism of Rev
function, Rev-RRE interaction, as well as inhibitors hereof
are reviewed.
[Back to top]
Rosuvastatin, Pravastatin, and Atorvastatin
for the Treatment of Hypercholesterolaemia in HIV-Infected
Patients Receiving Protease Inhibitors
Leonardo Calza,
Roberto Manfredi, Vincenzo
Colangeli, Daria Pocaterra, Michele Pavoni and Francesco Chiodo
Highly active antiretroviral therapy (HAART) including protease
inhibitors (PIs) has been independently associated with an
abnormal lipid profile, and recent studies have shown an increased
risk of cardiovascular complications in patients with prolonged
exposure to HAART. Aim of our open-label, randomized, prospective
study is to evaluate the role of different statins in the
management of PI-associated hypercholesterolaemia. Ninety-four
adult patients on a stable PI-based antiretroviral therapy
since at least 12 months, and presenting hypercholesterolaemia
(total cholesterol level >250 mg/dL) of at least 3-month
duration and unresponsive to a hypolipidaemic diet and physical
exercise, were randomized to a hypolipidaemic treatment with
rosuvastatin (10 mg once daily), pravastatin (20 mg once daily)
or atorvastatin (10 mg once daily), and were followed-up for
12 months. Among the 85 subjects who completed the study,
rosuvastatin was employed in 26 cases, pravastatin in 31,
and atorvastatin in 28. At the close of 1-year follow-up,
statins led to a mean reduction of 21.2% and 23.6% versus
baseline total cholesterol and LDL cholesterol levels, respectively
(p=0.002). Mean decrease in total cholesterol concentration
was significantly greater with rosuvastatin (25.2%) than with
pravastatin (17.6%; p=0.01) and atorvastatin (19.8%; p=0.03).
During these 12 months, all administered statins showed a
favourable tolerability profile, and patients’ plasma
HIV viral load did not present any variation. All used statins
showed a significant efficacy and a good tolerability in the
treatment of diet-resistant hyperlipidaemia, but rosuvastatin
was found to be more effective in reducing total and LDL cholesterol
levels. |
