scholarly journals Molecularly cloned SHIV-CN97001: a replication-competent, R5 simian/human immunodeficiency virus containing env of a primary Chinese HIV-1 clade C isolate

2011 ◽  
Vol 40 (6) ◽  
pp. 427-436 ◽  
Author(s):  
Qiang Liu ◽  
Yue Li ◽  
GuiBo Yang ◽  
JieJie Dai ◽  
Ruth M. Ruprecht ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Hiv 1

scholarly journals Favorable and Unfavorable HLA Class I Alleles and Haplotypes in Zambians Predominantly Infected with Clade C Human Immunodeficiency Virus Type 1

2002 ◽  
Vol 76 (16) ◽  
pp. 8276-8284 ◽  
Author(s):  
Jianming Tang ◽  
Shenghui Tang ◽  
Elena Lobashevsky ◽  
Angela D. Myracle ◽  
Ulgen Fideli ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Hla Class I ◽  
Class I ◽  
Hla Class I Molecules ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Hiv 1

ABSTRACT The setpoint of viral RNA concentration (viral load [VL]) during chronic human immunodeficiency virus type 1 (HIV-1) infection reflects a virus-host equilibration closely related to CD8+ cytotoxic T-lymphocyte (CTL) responses, which rely heavily on antigen presentation by the human major histocompatibility complex (MHC) (i.e., HLA) class I molecules. Differences in HIV-1 VL among 259 mostly clade C virus-infected individuals (137 females and 122 males) in the Zambia-UAB HIV Research Project (ZUHRP) were associated with several HLA class I alleles and haplotypes. In particular, general linear model analyses revealed lower log10 VL among those with HLA allele B*57 (P = 0.002 [without correction]) previously implicated in favorable response and in those with HLA B*39 and A*30-Cw*03 (P = 0.002 to 0.016); the same analyses also demonstrated higher log10 VL among individuals with A*02-Cw*16, A*23-B*14, and A*23-Cw*07 (P = 0.010 to 0.033). These HLA effects remained strong (P = 0.0002 to 0.075) after adjustment for age, gender, and duration of infection and persisted across three orders of VL categories (P = 0.001 to 0.084). In contrast, neither B*35 (n = 15) nor B*53 (n = 53) showed a clear disadvantage such as that reported elsewhere for these closely related alleles. Other HLA associations with unusually high (A*68, B*41, B*45, and Cw*16) or low (B*13, Cw*12, and Cw*18) VL were either unstable or reflected their tight linkage respecting disequilibria with other class I variants. The three consistently favorable HLA class I variants retained in multivariable models and in alternative analyses were present in 30.9% of subjects with the lowest (<10,000 copies per ml) and 3.1% of those with the highest (>100,000) VL. Clear differential distribution of HLA profiles according to level of viremia suggests important host genetic contribution to the pattern of immune control and escape during HIV-1 infection.

scholarly journals Identification and Characterization of a New Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Human Monoclonal Antibody

2004 ◽  
Vol 78 (17) ◽  
pp. 9233-9242 ◽  
Author(s):  
Mei-Yun Zhang ◽  
Xiaodong Xiao ◽  
Igor A. Sidorov ◽  
Vidita Choudhry ◽  
Fatim Cham ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Human Antibody ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Identification And Characterization ◽  
Hiv 1 ◽  
Soluble Cd4

ABSTRACT The identification and characterization of new human monoclonal antibodies (hMAbs) able to neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates from different subtypes may help in our understanding of the mechanisms of virus entry and neutralization and in the development of entry inhibitors and vaccines. For enhanced selection of broadly cross-reactive antibodies, soluble HIV-1 envelope glycoproteins (Envs proteins) from two isolates complexed with two-domain soluble CD4 (sCD4) were alternated during panning of a phage-displayed human antibody library; these two Env proteins (89.6 and IIIB gp140s), and one additional Env (JR-FL gp120) alone and complexed with sCD4 were used for screening. An antibody with relatively long HCDR3 (17 residues), designated m14, was identified that bound to all antigens and neutralized heterologous HIV-1 isolates in multiple assay formats. Fab m14 potently neutralized selected well-characterized subtype B isolates, including JRCSF, 89.6, IIIB, and Yu2. Immunoglobulin G1 (IgG1) m14 was more potent than Fab m14 and neutralized 7 of 10 other clade B isolates; notably, although the potency was on average significantly lower than that of IgG1 b12, IgG1 m14 neutralized two of the isolates with significantly lower 50% inhibitory concentrations than did IgG1 b12. IgG1 m14 neutralized four of four selected clade C isolates with potency higher than that of IgG1 b12. It also neutralized 7 of 17 clade C isolates from southern Africa that were difficult to neutralize with other hMAbs and sCD4. IgG1 m14 neutralized four of seven primary HIV-1 isolates from other clades (A, D, E, and F) much more efficiently than did IgG1 b12; for the other three isolates, IgG b12 was much more potent. Fab m14 bound with high (nanomolar range) affinity to gp120 and gp140 from various isolates; its binding was reduced by soluble CD4 and antibodies recognizing the CD4 binding site (CD4bs) on gp120, and its footprint as defined by alanine-scanning mutagenesis overlaps that of b12. These results suggest that m14 is a novel CD4bs cross-reactive HIV-1-neutralizing antibody that exhibits a different inhibitory profile compared to the only known potent broadly neutralizing CD4bs human antibody, b12, and may have implications for our understanding of the mechanisms of immune evasion and for the development of inhibitors and vaccines.

scholarly journals Laboratory characteristics of HIV-1 clade C-infected long-term non-progressors at a tertiary human immunodeficiency virus care centre in South India

2008 ◽  
Vol 57 (7) ◽  
pp. 913-915
Author(s):  
Uma Shanmugasundaram ◽  
Kailapuri G. Murugavel ◽  
Esaki Muthu Shankar ◽  
Pachamuthu Balakrishnan ◽  
Suniti Solomon ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
South India ◽  
Human Immunodeficiency Virus Care ◽  
Care Centre ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Hiv 1

scholarly journals Differential Outcomes following Optimization of Simian-Human Immunodeficiency Viruses from Clades AE, B, and C

2020 ◽  
Vol 94 (10) ◽  
Author(s):  
Lawrence J. Tartaglia ◽  
Siddhant Gupte ◽  
Kevin C. Pastores ◽  
Sebastien Trott ◽  
Peter Abbink ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Rhesus Monkeys ◽  
Replicative Capacity ◽  
Wild Type ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Hiv 1

ABSTRACT Simian-human immunodeficiency virus (SHIV) infection of rhesus monkeys is an important preclinical model for human immunodeficiency virus type 1 (HIV-1) vaccines, therapeutics, and cure strategies. SHIVs have been optimized by incorporating HIV-1 Env residue 375 mutations that mimic the bulky or hydrophobic residues typically found in simian immunodeficiency virus (SIV) Env to improve rhesus CD4 binding. We applied this strategy to three SHIV challenge stocks (SHIV-SF162p3, SHIV-AE16, and SHIV-325c) and observed three distinct outcomes. We constructed six Env375 variants (M, H, W, Y, F, and S) for each SHIV, and we performed a pool competition study in rhesus monkeys to define the optimal variant for each SHIV prior to generating large-scale challenge stocks. We identified SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH as the optimal variants. SHIV-SF162p3S could not be improved, as it already contained the optimal Env375 residue. SHIV-AE16W exhibited a similar replicative capacity to the parental SHIV-AE16 stock. In contrast, SHIV-325cH demonstrated a 2.6-log higher peak and 1.6-log higher setpoint viral loads than the parental SHIV-325c stock. These data demonstrate the diversity of potential outcomes following Env375 modification in SHIVs. Moreover, the clade C SHIV-325cH challenge stock may prove useful for evaluating prophylactic or therapeutic interventions against clade C HIV-1. IMPORTANCE We sought to enhance the infectivity of three SHIV stocks by optimization of a key residue in human immunodeficiency virus type 1 (HIV-1) Env (Env375). We developed the following three new simian-human immunodeficiency virus (SHIV) stocks: SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH. SHIV-SF162p3S could not be optimized, SHIV-AE16W proved comparable to the parental virus, and SHIV-325cH demonstrated markedly enhanced replicative capacity compared with the parental virus.

scholarly journals Generation and Evaluation of Clade C Simian-Human Immunodeficiency Virus Challenge Stocks

2014 ◽  
Vol 89 (4) ◽  
pp. 1965-1974 ◽  
Author(s):  
Hui-Wen Chang ◽  
Lawrence J. Tartaglia ◽  
James B. Whitney ◽  
So-Yon Lim ◽  
Srisowmya Sanisetty ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Rhesus Monkeys ◽  
Acute Infection ◽  
High Dose ◽  
Mucosal Transmission ◽  
Preclinical Evaluation ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Hiv 1

ABSTRACTThe development of a panel of mucosally transmissible simian-human immunodeficiency virus (SHIV) challenge stocks from multiple virus clades would facilitate preclinical evaluation of candidate HIV-1 vaccines and therapeutics. The majority of SHIV stocks that have been generated to date have been derived from clade B HIV-1envsequences from viruses isolated during chronic infection and typically required serial animal-to-animal adaptation for establishing mucosal transmissibility and pathogenicity. To capture essential features of mucosal transmission of clade C viruses, we produced a series of SHIVs with early clade C HIV-1envsequences from acutely HIV-1-infected individuals from South Africa. SHIV-327c and SHIV-327cRM expressedenvsequences that were 99.7 to 100% identical to the original HIV-1 isolate and did not requirein vivopassaging for mucosal infectivity. These challenge stocks infected rhesus monkeys efficiently by both intrarectal and intravaginal routes, replicated to high levels during acute infection, and established chronic setpoint viremia in 13 of 17 (76%) infected animals. The SHIV-327cRM challenge stock was also titrated for both single, high-dose intrarectal challenges and repetitive, low-dose intrarectal challenges in rhesus monkeys. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines and other interventions aimed at preventing clade C HIV-1 infection.IMPORTANCEWe describe the development of two related clade C SHIV challenge stocks. These challenge stocks should prove useful for preclinical testing of vaccines and other interventions aimed at preventing clade C HIV-1 infection.

scholarly journals Infectious Molecular Clone of a Recently Transmitted Pediatric Human Immunodeficiency Virus Clade C Isolate from Africa: Evidence of Intraclade Recombination

2004 ◽  
Vol 78 (24) ◽  
pp. 14066-14069 ◽  
Author(s):  
Ricky D. Grisson ◽  
Agnès-Laurence Chenine ◽  
Lan-Yu Yeh ◽  
Jun He ◽  
Charles Wood ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Vaccine Development ◽  
Infectious Molecular Clone ◽  
Molecular Clone ◽  
Development Tool ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Hiv 1

ABSTRACT Although human immunodeficiency virus type 1 (HIV-1) clade C continues to dominate the pandemic, only two infectious clade C proviral DNA clones have been described (N. Mochizuki, N. Otsuka, K. Matsuo, T. Shiino, A. Kojima, T. Kurata, K. Sakai, N. Yamamoto, S. Isomura, T. N. Dhole, Y. Takebe, M. Matsuda, and M. Tatsumi, AIDS Res. Hum. Retrovir. 15:1321-1324, 1999; T. Ndung'u, B. Renjifo, and M. Essex, J. Virol. 75:4964-4972, 2001). We have generated an infectious molecular clone of a pediatric clade C strain, HIV1084i, which was isolated from a Zambian infant infected either intrapartum or through breastfeeding. HIV1084i is an R5, non-syncytium-inducing isolate that bears all known clade C signatures; gag, pol, and env consistently mapped within clade C. Interestingly, gag resembled Asian isolates, whereas pol and env resembled African isolates, indicating that HIV1084i probably arose from an intraclade recombination. As a recently transmitted clade C strain, HIV1084i will be a useful vaccine development tool.

scholarly journals Relative Transmissibility of an R5 Clade C Simian‐Human Immunodeficiency Virus Across Different Mucosae in Macaques Parallels the Relative Risks of Sexual HIV‐1 Transmission in Humans via Different Routes

2010 ◽  
Vol 201 (8) ◽  
pp. 1155-1163 ◽  
Author(s):  
Agnès L. Chenine ◽  
Nagadenahalli B. Siddappa ◽  
Victor G. Kramer ◽  
Gaia Sciaranghella ◽  
Robert A. Rasmussen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Relative Risks ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Hiv 1

scholarly journals Molecularly Cloned SHIV-1157ipd3N4: a Highly Replication- Competent, Mucosally Transmissible R5 Simian-Human Immunodeficiency Virus Encoding HIV Clade C env

2006 ◽  
Vol 80 (17) ◽  
pp. 8729-8738 ◽  
Author(s):  
R. J. Song ◽  
A.-L. Chenine ◽  
R. A. Rasmussen ◽  
C. R. Ruprecht ◽  
S. Mirshahidi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Mononuclear Cells ◽  
Cell Depletion ◽  
Peripheral Blood Mononuclear ◽  
T Cell Depletion ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Aids Vaccines ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) clade C causes >50% of all HIV infections worldwide, and an estimated 90% of all transmissions occur mucosally with R5 strains. A pathogenic R5 simian-human immunodeficiency virus (SHIV) encoding HIV clade C env is highly desirable to evaluate candidate AIDS vaccines in nonhuman primates. To this end, we generated SHIV-1157i, a molecular clone from a Zambian infant isolate that carries HIV clade C env. SHIV-1157i was adapted by serial passage in five monkeys, three of which developed peripheral CD4+ T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, transfer of its infected blood to a naïve animal induced memory T-cell depletion and thrombocytopenia within 3 months in the recipient. In parallel, genomic DNA from the blood donor was amplified to generate the late proviral clone SHIV-1157ipd3. To increase the replicative capacity of SHIV-1157ipd3, an extra NF-κB binding site was engineered into its 3′ long terminal repeat, giving rise to SHIV-1157ipd3N4. This virus was exclusively R5 tropic and replicated more potently in rhesus peripheral blood mononuclear cells than SHIV-1157ipd3 in the presence of tumor necrosis factor alpha. Rhesus macaques of Indian and Chinese origin were next inoculated intrarectally with SHIV-1157ipd3N4; this virus replicated vigorously in both sets of monkeys. We conclude that SHIV-1157ipd3N4 is a highly replication-competent, mucosally transmissible R5 SHIV that represents a valuable tool to test candidate AIDS vaccines targeting HIV-1 clade C Env.

Sign in / Sign up

Export Citation Format

Share Document