Immunogenic Comparison of Chimeric Adenovirus 5/35 Vector Carrying Optimized Human Immunodeficiency Virus Clade C Genes and Various Promoters

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.

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Characterization of Human Immunodeficiency Virus (HIV)-Infected Cells in Infiltrates Associated With CNS Opportunistic Infections in Patients With HIV Clade C Infection

Journal of Neuropathology & Experimental Neurology ◽

10.1097/nen.0b013e3181461d3e ◽

2007 ◽

Vol 66 (9) ◽

pp. 799-808 ◽

Cited By ~ 14

Author(s):

Anita Mahadevan ◽

Susarla K. Shankar ◽

Parthasarathy Satishchandra ◽

Udaykumar Ranga ◽

Yasha Thagadur Chickabasaviah ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Opportunistic Infections ◽

Immunodeficiency Virus ◽

Clade C ◽

Infected Cells

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

Journal of Virology ◽

10.1128/jvi.78.17.9233-9242.2004 ◽

2004 ◽

Vol 78 (17) ◽

pp. 9233-9242 ◽

Cited By ~ 63

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.

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

Journal of Medical Primatology ◽

10.1111/j.1600-0684.2011.00497.x ◽

2011 ◽

Vol 40 (6) ◽

pp. 427-436 ◽

Cited By ~ 4

Author(s):

Qiang Liu ◽

Yue Li ◽

GuiBo Yang ◽

JieJie Dai ◽

Ruth M. Ruprecht ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immunodeficiency Virus ◽

Clade C ◽

Hiv 1

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Estimation of virological and immunological parameters in subjects from South India infected with human immunodeficiency virus type 1 clade C and correlation of findings with occurrence of neurological disease

Journal of NeuroVirology ◽

10.1080/13550280802338652 ◽

2009 ◽

Vol 15 (1) ◽

pp. 25-35 ◽

Cited By ~ 4

Author(s):

Anupa Kamat ◽

V Ravi ◽

Anita Desai ◽

P Satishchandra ◽

KS Satish ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Neurological Disease ◽

South India ◽

Immunological Parameters ◽

Immunodeficiency Virus ◽

Clade C

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Characterization of a Virtually Full-Length Human Immunodeficiency Virus Type 1 Genome of a Prevalent Intersubtype (C/B′) Recombinant Strain in China

Journal of Virology ◽

10.1128/jvi.74.23.11367-11376.2000 ◽

2000 ◽

Vol 74 (23) ◽

pp. 11367-11376 ◽

Cited By ~ 220

Author(s):

Ling Su ◽

Marcus Graf ◽

Yuanzhi Zhang ◽

Hagen von Briesen ◽

Hui Xing ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Subtype C ◽

Coding Region ◽

Immunodeficiency Virus ◽

Clade C ◽

Region Ii ◽

Virus Strains

ABSTRACT A molecular epidemiology study was conducted among more than 100 human immunodeficiency virus type 1 (HIV-1) subtype C seropositive intravenous drug users (IDUs) from China. Genotyping based on the envelope C2V3 coding region revealed the highest homology of the most prevalent virus strains circulating throughout China to subtype C sequences of Indian origin. Based on these results, a virtually full-length genome representing the most prevalent class of clade C strains circulating throughout China was directly amplified from peripheral blood mononuclear cells of a selected HIV-infected IDU and subcloned. Sequence analysis identified a mosaic structure, suggesting extensive intersubtype recombination events between genomes of the prevalent clade C and (B′)-subtype Thai virus strains of that geographic region. Recombinant Identification Program analysis and phylogenetic bootstrapping suggested that there were 10 breakpoints (i) in the gag-pol coding region, (ii) in vpr and at the 3′ end of the vpu gene, and (iii) in thenef open reading frame. (B′)-sequences therefore include (i) several insertions in the gag-pol coding region; (ii) 3′-vpr, the complete vpu gene, and the first exons of tat and rev; and (iii) the 5′ half of the nef gene. Breakpoints located in thevpr/vpu coding region as well as in the nefgene of 97cn54 were found at almost identical positions of all subtype C strains isolated from IDUs living in different areas of China, suggesting a common ancestor for the C/B′ recombinant strains. More than 50% of well-defined subtype B-derived cytotoxic T-lymphocyte epitopes within Gag and Pol and 10% of the known epitopes in Env were found to exactly match sequences within in this clade C/B′ chimeric reference strain. These results may substantially facilitate a biological comparison of clade C-derived reference strains as well as the generation of useful reagents supporting vaccine-related efforts in China.

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Coinfection with Schistosoma mansoni Reactivates Viremia in Rhesus Macaques with Chronic Simian-Human Immunodeficiency Virus Clade C Infection

Infection and Immunity ◽

10.1128/iai.01703-06 ◽

2007 ◽

Vol 75 (4) ◽

pp. 1751-1756 ◽

Cited By ~ 27

Author(s):

Mila Ayash-Rashkovsky ◽

Agnès-Laurence Chenine ◽

Lisa N. Steele ◽

Sandra J. Lee ◽

Ruijiang Song ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Replication ◽

Schistosoma Mansoni ◽

Rhesus Macaques ◽

Cell Subset ◽

Interleukin 4 ◽

Immunodeficiency Virus ◽

Clade C

ABSTRACT We tested the hypothesis that helminth parasite coinfection would intensify viremia and accelerate disease progression in monkeys chronically infected with an R5 simian-human immunodeficiency virus (SHIV) encoding a human immunodeficiency virus type 1 (HIV-1) clade C envelope. Fifteen rhesus monkeys with stable SHIV-1157ip infection were enrolled into a prospective, randomized trial. These seropositive animals had undetectable viral RNA and no signs of immunodeficiency. Seven animals served as virus-only controls; eight animals were exposed to Schistosoma mansoni cercariae. From week 5 after parasite exposure onward, coinfected animals shed eggs in their feces, developed eosinophilia, and had significantly higher mRNA expression of the T-helper type 2 cytokine interleukin-4 (P = 0.001) than animals without schistosomiasis. Compared to virus-only controls, viral replication was significantly increased in coinfected monkeys (P = 0.012), and the percentage of their CD4+ CD29+ memory cells decreased over time (P = 0.05). Thus, S. mansoni coinfection significantly increased viral replication and induced T-cell subset alterations in monkeys with chronic SHIV clade C infection.

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