scholarly journals Human Immunodeficiency Virus Type 1 Disease Progression, CCR5 Genotype, and Specific Immune Responses

1998 ◽  
Vol 5 (4) ◽  
pp. 463-466 ◽  
Author(s):  
Ubaldo Visco-Comandini ◽  
Catharina Hultgren ◽  
Christina Broström ◽  
Markus Birk ◽  
Soo Kim ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Cell Count ◽  
Disease Progression ◽  
Wild Type ◽  
Cd4 Cell Count ◽  
Immunodeficiency Virus ◽  
Cd4 Cell ◽  
Hiv 1

ABSTRACT The correlation among the presence of a 32-bp deletion in the CC-chemokine receptor 5 (CCR5) gene, disease progression, and human immunodeficiency virus type 1 (HIV-1)-specific immune responses was analyzed for a cohort of 79 Caucasian HIV-1-infected patients. The CCR5 genotype (CCR5/CCR5 = wild type/wild type or Δ32CCR5/CCR5 = 32-bp deletion/wild type) in peripheral blood mononuclear cells was determined by PCR, followed by sequencing of both wild-type and Δ32CCR5 gene fragments. HIV-1-specific humoral responses to gp41 and V3MN peptides were determined by enzyme immunoassays. The prevalence of the Δ32CCR5 allele was lower among 37 patients with rapid progression (progression to AIDS or to a CD4 cell count of <200 × 106/liter in less than 9 years; P < 0.01) compared to that for 42 patients with slow progression (no AIDS and CD4 cell count of >200 × 106/liter after at least 9 years from infection) or to that for 25 non-HIV-1-infected Swedish blood donors (P < 0.05). No differences were observed in the wild-type CCR5sequences between the different groups of patients. For three analyzed patients, the 32-bp Δ32CCR5 gene deletions were identical. The antibody titers against gp41 and a V3MNpeptide in patients with the Δ32CCR5/CCR5 genotype were not significantly different from those in pair-matchedCCR5/CCR5 controls. However, in 13 analyzed patients, a stronger serum neutralizing activity was associated with the Δ32CCR5/CCR5 genotype. Thus, a CCR5/CCR5genotype correlates with a shortened AIDS-free HIV-1 infection period and possibly with a worse neutralizing activity, without an evident influence on the antibody response to two major antigenic regions of HIV-1 envelope.

scholarly journals Treatment with the Fusion Inhibitor Enfuvirtide Influences the Appearance of Mutations in the Human Immunodeficiency Virus Type 1 Regulatory Protein Rev

2009 ◽  
Vol 53 (7) ◽  
pp. 2816-2823 ◽  
Author(s):  
Valentina Svicher ◽  
Claudia Alteri ◽  
Roberta D'Arrigo ◽  
Alessandro Laganà ◽  
Maria Trignetti ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Life Cycle ◽  
Cell Count ◽  
Regulatory Protein ◽  
Fusion Inhibitor ◽  
Cd4 Cell Count ◽  
Immunodeficiency Virus ◽  
Cd4 Cell ◽  
Hiv 1

ABSTRACT The gp41-encoding sequence of the env gene contains in two separate regions the Rev-responsive elements (RRE) and the alternative open reading frame of the second exon of the regulatory protein Rev. The binding of Rev to the RRE allows the transport of unspliced/singly spliced viral mRNAs out of the nucleus, an essential step in the life cycle of human immunodeficiency virus type 1 (HIV-1). In this study, we have investigated whether the fusion-inhibitor enfuvirtide (ENF) can induce mutations in Rev and if these mutations correlate with the classical ENF resistance gp41 mutations and with viremia and CD4 cell count. Specific Rev mutations were positively associated with ENF treatment and significantly correlated with classical ENF resistance gp41 mutations. In particular, a cluster was observed for the Rev mutations E57A (E57Arev) and N86Srev with the ENF resistance gp41 mutations Q40H (Q40Hgp41) and L45Mgp41. In addition, the presence at week 48 of the E57Arev correlates with a significant viremia increase from baseline to week 48 and with a CD4 cell count loss from baseline to week 48. By modeling the RRE structure, we found that the Q40gp41 and L45gp41 codons form complementary base pairs in a region of the RRE involved in Rev binding. The conformation of this Rev-binding site is disrupted when Q40Hgp41 and L45Mgp41 occur alone while it is restored when both mutations are present. In conclusion, our study shows that ENF pressure may also affect both Rev and RRE structures and can provide an excellent example of compensatory evolution. This highlights the multiple roles of ENF (and perhaps other entry inhibitors) in modulating the correct interplay between the different HIV-1 genes and proteins during the HIV-1 life cycle.

scholarly journals Frequency of Cytomegalovirus Viral Load in Iranian Human Immunodeficiency Virus-1-Infected Patients with CD4+ Counts <100 Cells/mm3

Intervirology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Mohammad Reza Jabbari ◽  
Hoorieh Soleimanjahi ◽  
Somayeh Shatizadeh Malekshahi ◽  
Mohammad Gholami ◽  
Leila Sadeghi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Cell Count ◽  
Previous History ◽  
Cd4 Count ◽  
Cd4 Cell Count ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Cd4 Cell ◽  
Hiv 1

<b><i>Objectives:</i></b> The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count &#x3c;100 cells/mm<sup>3</sup> and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis. <b><i>Methods:</i></b> This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count &#x3c;100 cells/mm<sup>3</sup>, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD). <b><i>Results:</i></b> Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (<i>p</i> value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (<i>p</i> &#x3c; 0.02). <b><i>Conclusions:</i></b> We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count &#x3c;100 mm<sup>3</sup>/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD.

scholarly journals Neutralizing Antibodies against Autologous Human Immunodeficiency Virus Type 1 Isolates in Patients with Increasing CD4 Cell Counts despite Incomplete Virus Suppression during Antiretroviral Treatment

2001 ◽  
Vol 8 (4) ◽  
pp. 822-824 ◽  
Author(s):  
Loredana Sarmati ◽  
Gabriella d'Ettorre ◽  
Emanuele Nicastri ◽  
Lucia Ercoli ◽  
Ilaria Uccella ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Cell Count ◽  
Neutralizing Antibodies ◽  
Antiretroviral Treatment ◽  
Cd4 Cell Count ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Cd4 Cell

ABSTRACT Antiretroviral-treated human immunodeficiency virus (HIV) type 1-seropositive individuals can remain clinically stable for a long period of time with an increasing CD4 cell count irrespective of incomplete viral suppression. We evaluated the role of neutralizing antibody (NtAb) activity in the etiopathogenesis of this viro-immunological disconnection (defined as an increasing CD4+-cell count despite a persistent, detectable viral load during antiretroviral therapy) in 33 patients failing therapy with two analogue nucleoside reverse transcriptase inhibitors. An HIV NtAb titer of ≥1:25 was detected in specimens from 16 out of 33 (48%) patients. A significant correlation was found between NtAb titers and CD4+-cell counts (P = 0.001;r = 0.546) but not with HIV RNA levels in plasma. Five patients with a viro-immunological disconnection had an NtAb titer of >1:125, statistically higher than the NtAb titers for the remaining 28 patients with both virologic and immunologic failure (P < 0.0001). The HIV-specific humoral immune response could play a role during antiretroviral treatment to improve immunological function despite an incomplete suppression of viral load.

scholarly journals Relationships among the Detection of p24 Antigen, Human Immunodeficiency Virus (HIV) RNA Level, CD4 Cell Count, and Disease Progression in HIV‐Infected Individuals with Hemophilia

2001 ◽  
Vol 184 (4) ◽  
pp. 511-514 ◽  
Author(s):  
Caroline A. Sabin ◽  
Alessandro Cozzi Lepri ◽  
Helen Devereux ◽  
Andrew N. Phillips ◽  
Clive Loveday ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Count ◽  
Disease Progression ◽  
Cd4 Cell Count ◽  
Hiv Rna ◽  
Immunodeficiency Virus ◽  
P24 Antigen ◽  
Cd4 Cell

scholarly journals Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen

2006 ◽  
Vol 80 (14) ◽  
pp. 6745-6756 ◽  
Author(s):  
Eric A. Weaver ◽  
Zhongjing Lu ◽  
Zenaido T. Camacho ◽  
Fatiha Moukdar ◽  
Hua-Xin Liao ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Wild Type ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Subtype A ◽  
Hiv 1

ABSTRACT The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic group M consensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide sets from heterologous subtype A, B, and C viruses. The CON6-derived vaccine was immunogenic and induced a greater number of T-cell epitope responses than any single wild-type subtype A, B, and C env immunogen and similar T-cell responses to a polyvalent vaccine. The responses were comparable to within-clade responses but significantly more than between-clade responses. The magnitude of the T-cell responses induced by CON6 (measured by individual epitope peptides) was also greater than the magnitude of responses induced by individual wild-type env immunogens. Though the limited major histocompatibility complex repertoire in inbred mice does not necessarily predict responses in nonhuman primates and humans, these results suggest that synthetic centralized env immunogens represent a promising approach for HIV-1 vaccine design that merits further characterization.

scholarly journals Human immunodeficiency virus type 1 gp120 envelope characteristics associated with disease progression differ in family members infected with genetically similar viruses

2013 ◽  
Vol 94 (1) ◽  
pp. 20-29 ◽  
Author(s):  
Elly Baan ◽  
Renée M. van der Sluis ◽  
Margreet E. Bakker ◽  
Vincent Bekker ◽  
Dasja Pajkrt ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Positive Charge ◽  
Gp120 Envelope ◽  
Immunodeficiency Virus ◽  
Virus Strains ◽  
Hiv 1

The human immunodeficiency virus type 1 (HIV-1) envelope protein provides the primary contact between the virus and host, and is the main target of the adaptive humoral immune response. The length of gp120 variable loops and the number of N-linked glycosylation events are key determinants for virus infectivity and immune escape, while the V3 loop overall positive charge is known to affect co-receptor tropism. We selected two families in which both parents and two children had been infected with HIV-1 for nearly 10 years, but who demonstrated variable parameters of disease progression. We analysed the gp120 envelope sequence and compared individuals that progressed to those that did not in order to decipher evolutionary alterations that are associated with disease progression when individuals are infected with genetically related virus strains. The analysis of the V3-positive charge demonstrated an association between higher V3-positive charges with disease progression. The ratio between the amino acid length and the number of potential N-linked glycosylation sites was also shown to be associated with disease progression with the healthier family members having a lower ratio. In conclusion in individuals initially infected with genetically linked virus strains the V3-positive charges and N-linked glycosylation are associated with HIV-1 disease progression and follow varied evolutionary paths for individuals with varied disease progression.

scholarly journals Different Abilities of Escape Mutant-Specific Cytotoxic T Cells To Suppress Replication of Escape Mutant and Wild-Type Human Immunodeficiency Virus Type 1 in New Hosts

2007 ◽  
Vol 82 (1) ◽  
pp. 138-147 ◽  
Author(s):  
Mamoru Fujiwara ◽  
Junko Tanuma ◽  
Hirokazu Koizumi ◽  
Yuka Kawashima ◽  
Kazutaka Honda ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Escape Mutant ◽  
Wild Type ◽  
Specific Ctls ◽  
Immunodeficiency Virus ◽  
New Hosts ◽  
Hiv 1 ◽  
Hla Molecules

ABSTRACT There is much evidence that in human immunodeficiency virus type 1 (HIV-1)-infected individuals, strong cytotoxic T lymphocyte (CTL)-mediated immune pressure results in the selection of HIV-1 mutants that have escaped from wild-type-specific CTLs. If escape mutant-specific CTLs are not elicited in new hosts sharing donor HLA molecules, the transmission of these mutants results in the accumulation of escape mutants in the population. However, whether escape mutant-specific CTLs are definitively not elicited in new hosts sharing donor HLA molecules still remains unclear. A previous study showed that a Y-to-F substitution at the second position (2F) of the Nef138-10 epitope is significantly detected in HLA-A*2402+ hemophilic donors. Presently, we confirmed that this 2F mutant was an escape mutant by demonstrating strong and weak abilities of Nef138-10-specific CTL clones to suppress replication of the wild-type and 2F mutant viruses, respectively. We demonstrated the existence of the 2F-specific CTLs in three new hosts who had been primarily infected with the 2F mutant. The 2F-specific CTL clones suppressed the replication of both wild-type and mutant viruses. However, the abilities of these clones to suppress replication of the 2F virus were much weaker than those of wild-type-specific and the 2F-specific ones to suppress replication of the wild-type virus. These findings indicate that the 2F mutant is conserved in HIV-1-infected donors having HLA-A*2402, because the 2F-specific CTLs failed to completely suppress the 2F mutant replication and effectively prevented viral reversion in new hosts carrying HLA-A*2402.

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