Genetic diversity of the envelope glycoprotein from human immunodeficiency virus type 1 isolates of African origin

Although human immunodeficiency virus type 1 (HIV‐1) subtypes C and E are expanding faster and seem to be of greater global significance than HIV‐1 subtype B, there is only little information about Tat activity of such non‐B subtypes. Here, we showed evidence that subtype C Tat exhibits higher transcriptional activity from the HIV‐1 long‐terminal repeat (LTR) in a human T‐cell line, compared with subtypes B and E. This higher activity of subtype C Tat was not due to the LTR, but to the Tat sequence variability. We examined three candidate regions with sequence for the higher activity of subtype C Tat, such as the cysteine‐rich motif, the basic domain, and the 2nd exon. The results showed that the variation in subtype C Tat at two amino acid residues, Ser57 and Glu63 in stead of Arg57 and Gln63 in subtypes B and E, within and close to the basic domain were involved in the higher activity of subtype C Tat. This variation did not affect its nuclear localization activity. Thus, there may be a significant advantage for the high Tat activity on subtype C replication.

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“…The Ser 57 and Glu 63 were highly conserved among subtype C isolates reported previously (Fig. 5) (14,32,33,38,49,55).…”

Section: Involvement Of Two Amino Acids Within and Close To The Basicsupporting

confidence: 66%

Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Kurosu

Mukai

Komoto

et al. 2002

Microbiology and Immunology

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“…The best dataset resulted in 20 full-length env sequences sampled in 1992; they belong to the non-recombinant subtype A, B, C, D, and G of HIV-1 group M. We also retrieved all the available HIV-1 subtype B full-length env sequences with known sampling year and used these to estimate the evolutionary rate. In total, 59 HIV-1 entire envelope sequences with known sampling year between 1983 and 1996 were retrieved from the HIV database and SIVcpzGAB, SIVcpzUS, and HIV-O sequences were included as outgroups (2)(3)(4). Sequences were aligned with Clustal W, and all the gaps were removed from the final alignment.…”

Section: Sequence Datamentioning

confidence: 99%

Dating the common ancestor of SIVcpz and HIV‐1 group M and the origin of HIV‐1 subtypes by using a new method to uncover clock‐like molecular evolution

et al. 2000

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Attempts to estimate the time of origin of human immunodeficiency virus (HIV)-1 by using phylogenetic analysis are seriously flawed because of the unequal evolutionary rates among different viral lineages. Here, we report a new method of molecular clock analysis, called Site Stripping for Clock Detection (SSCD), which allows selection of nucleotide sites evolving at an equal rate in different lineages. The method was validated on a dataset of patients all infected with hepatitis C virus in 1977 by the same donor, and it was able to date exactly the known origin of the infection. Using the same method, we calculated that the origin of HIV-1 group M radiation was in the 1930s. In addition, we show that the coalescence time of the simian ancestor of HIV-1 group M and its closest related cpz strains occurred around the end of the XVII century, a date that could be considered the upper limit to the time of simian-to-human transmission of HIV-1 group M. The results show also that SSCD is an easy-to-use method of general applicability in molecular evolution to calibrate clock-like phylogenetic trees.

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“…The subtype of the env genes of the Group M strains, CA1 , VI525 [Louwagie et al, 1995], CA13 [Janssens et al, in press], CA4, CA5, CA10, CA20, CI13, VI191, VI313, VI526 was determined by sequence analysis of the full env-gene (unpublished results); for VI829 a heteroduplex mobility assay, using a 700 bp fragment overlapping the V3 till V5 region, was carried out [Delwart et al, 1993]. To characterize the Group O strains, CA9 and VI686, the full env-gene sequence was used .…”

Section: Phylogenetic Characterization Of Hiv-1 Virus Isolatesmentioning

confidence: 99%

Identification and characterization of sera from HIV-infected individuals with broad cross-neutralizing activity against group M (env clade A-H) and group O primary HIV-1 isolates

et al. 2000

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A previous study on cross-clade neutralization activity, identified three key isolates, MNlab (envB/gagB; X4 coreceptor), VI525 (envG/gagH, envA/gagA; R5X4) and CA9 (Group O; R5), that allowed discrimination of sera, likely or unlikely to neutralize primary HIV-1 isolates belonging to Group M (env clades A-H) and Group O. The prognostic ability of these three isolates was verified by means of an external validation on a different and larger set of sera. A total of 79 different sera (66 HIV-1, 10 HIV-2, 1 HIV-1+2 and 2 SIV(cpz)) were examined first for their capacity to neutralize the three key isolates, next sera were challenged against 12 other primary HIV-1 isolates of Group M (env A-H) and 2 isolates of Group O. Sera that neutralized all three isolates with an ID(50) titer of > or =1/40, also neutralized the 14 other primary isolates belonging to different genetic groups and clades. Sera that did not neutralize all three isolates did not exert broad cross-neutralizing activity. The neutralizing activity was antibody-mediated because it was absorbed and eluted from a Prot-G column. Competition-neutralization experiments using recombinant gp120 (HIV-1 MNlab) reduced the neutralizing capacity, suggesting that the neutralizing antibodies were directed against the Env protein. Remarkably, the broad cross-neutralization activity was found primarily in African female patients. In conclusion, this study confirms that three isolates are sufficient to allow identification of broad cross-neutralizing sera.

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Genetic diversity of the envelope glycoprotein from human immunodeficiency virus type 1 isolates of African origin

Abstract: The genetic diversity of the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) isolates was studied. HIV-1 isolates were obtained from eight countries in Africa: Djibouti,

Cited by 180 publications

References 36 publications

Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Dating the common ancestor of SIVcpz and HIV‐1 group M and the origin of HIV‐1 subtypes by using a new method to uncover clock‐like molecular evolution

Identification and characterization of sera from HIV-infected individuals with broad cross-neutralizing activity against group M (env clade A-H) and group O primary HIV-1 isolates

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