Sequence analysis of HIV-1 isolates from Guinea-Bissau: selection of vaccine epitopes relevant in both West African and European countries

Vinner, Lasse; Holmgren, Birgitta; Jensen, Kristoffer Jarlov; Esbjörnsson, Joakim; Borggren, Marie; Hentze, Julie L.; Karlsson, Ingrid; Andresen, Betina S; Gram, Gregers J.; Kløverpris, Henrik N.; Aaby, Péter; Silva, Zacarias José da; Fenyõ, Éva Mária; Fomsgaard, Anders

doi:10.1111/j.1600-0463.2011.02763.x

Cited by 8 publications

(5 citation statements)

References 52 publications

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“…For the analyses of the neutralizing activity of HIV-positive plasma, two HIV isolates, one HIV-1 and one HIV-2, were used. The HIV-1 circulating recombinant form (CRF)02_AG isolate, AG GB/30, originated from the same Guinea-Bissau study population from which the analyzed plasma was obtained (9,30). The HIV-2 subtype A isolate, A WA/P1-1991, originated from West Africa (10) and was isolated by cocul- (10) with reagents from Jackson Immunotech (Marseille, France).…”

Section: Methodsmentioning

confidence: 99%

“…The HIV-1 subtype CRF02 (AG), GB/30, was isolated from plasma based on the method of Costa et al (32) and was described in detail previously (30). The two isolates included in the present study were tested for coreceptor use on the U87.CD4 indicator cell lines and were found to use CCR5 for cell entry, which was our rationale for the use of U87.CD4.CCR5 cells as targets in the neutralization assays (9,10,33,34).…”

Section: Methodsmentioning

confidence: 99%

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Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent

Şahin

Holmgren

Sheik-Khalil

et al. 2013

J Virol

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Human immunodeficiency virus type 2 (HIV-2)-infected individuals develop immunodeficiency with a considerable delay andtransmit the virus at rates lower than HIV-1-infected persons. Conceivably, comparative studies on the immune responsiveness of HIV-1-and HIV-2-infected hosts may help to explain the differences in pathogenesis and transmission between the two types of infection. Previous studies have shown that the neutralizing antibody response is more potent and broader in HIV-2 than in HIV-1 infection. In the present study, we have examined further the function of the humoral immune response and studied the effect of complement on the antiviral activity of plasma from singly HIV-1-or HIV-2-infected individuals, as well as HIV-1/ HIV-2 dually infected individuals. The neutralization and antibody-dependent complement-mediated inactivation of HIV-1 and HIV-2 isolates were tested in a plaque reduction assay using U87.CD4.CCR5 cells. The results showed that the addition of complement increased intratype antiviral activities of both HIV-1 and HIV-2 plasma samples, although the complement effect was more pronounced with HIV-2 than HIV-1 plasma. Using an area-under-the-curve (AUC)-based readout, multivariate statistical analysis confirmed that the type of HIV infection was independently associated with the magnitude of the complement effect. The analyses carried out with purified IgG indicated that the complement effect was largely exerted through the classical complement pathway involving IgG in both HIV-1 and HIV-2 infections. In summary, these findings suggest that antibody binding to HIV-2 structures facilitates the efficient use of complement and thereby may be one factor contributing to a strong antiviral activity present in HIV-2 infection.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent

Şahin

Holmgren

Sheik-Khalil

et al. 2013

J Virol

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“…We next aligned the sequence reads from our lion and perch samples against their corresponding retroviral contigs and calculated the nucleotide diversity as well as the minor allele frequency. To estimate an upper level of genetic variation found in exogenous retroviruses, we obtained DNA sequence reads from in vitro cultures with two different strains of HIV, Bx08 and CC0030 19 20 . A combination of high mutation rate, short generation time, and recombination makes HIV the retrovirus with the highest level of known intra-host genetic variation 21 22 , and thus suitable as a representative exogenous retrovirus against which to compare retroviral sequences of unknown origin.…”

Section: Resultsmentioning

confidence: 99%

Characterizing novel endogenous retroviruses from genetic variation inferred from short sequence reads

Mourier

Mollerup

Vinner

et al. 2015

Sci Rep

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From Illumina sequencing of DNA from brain and liver tissue from the lion, Panthera leo, and tumor samples from the pike-perch, Sander lucioperca, we obtained two assembled sequence contigs with similarity to known retroviruses. Phylogenetic analyses suggest that the pike-perch retrovirus belongs to the epsilonretroviruses, and the lion retrovirus to the gammaretroviruses. To determine if these novel retroviral sequences originate from an endogenous retrovirus or from a recently integrated exogenous retrovirus, we assessed the genetic diversity of the parental sequences from which the short Illumina reads are derived. First, we showed by simulations that we can robustly infer the level of genetic diversity from short sequence reads. Second, we find that the measures of nucleotide diversity inferred from our retroviral sequences significantly exceed the level observed from Human Immunodeficiency Virus infections, prompting us to conclude that the novel retroviruses are both of endogenous origin. Through further simulations, we rule out the possibility that the observed elevated levels of nucleotide diversity are the result of co-infection with two closely related exogenous retroviruses.

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“…Collected blood samples has enabled in-depth studies of virological and immunological correlates of HIV-1 and HIV-2-related disease [3,[27][28][29][30][31][32][33][34][35][36][37][38].…”

Section: The Police Cohortmentioning

confidence: 99%

“…HIV-1, 11% HIV-2, 8% HIV-1/2 and 17% with unknown HIV-type) and is unique because it comprises the world's largest single-center cohort of HIV-2 and HIV-1/2 dually infected patients. The median age at time of inclusion is 36 years (interquartile range [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] with the majority of patients being female (63%). Other infections are coprevalent in Guinea-Bissau, including tuberculosis [39], HTLV-1 [40][41][42] and hepatitis [43,44], creating a unique opportunity to study different co-infections' effect on disease progression, immune response and response to treatment.…”

Section: The Bissau Hiv Cohortmentioning

confidence: 99%

HIV treatment in Guinea-Bissau: room for improvement and time for new treatment options

et al. 2020

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Despite advances in the treatment quality of HIV throughout the world, several countries are still facing numerous obstacles in delivering HIV treatment at a sufficiently high quality, putting patients’ lives in jeopardy. The aim of this status article is to give an overview of HIV treatment outcomes in the West African country, Guinea-Bissau, and to assess how newer treatment strategies such as long-acting injectable drugs or an HIV cure may limit or stop the HIV epidemic in this politically unstable and low-resource setting. Several HIV cohorts in Guinea-Bissau have been established and are used as platforms for epidemiological, virological, immunological and clinical studies often with a special focus on HIV-2, which is prevalent in the country. The Bandim Health Project, a demographic surveillance site, has performed epidemiological HIV surveys since 1987 among an urban population in the capital Bissau. The Police cohort, an occupational cohort of police officers, has enabled analyses of persons seroconverting with estimated times of seroconversion among HIV-1 and HIV-2-infected individuals, allowing incidence measurements while the Bissau HIV Cohort and a newer Nationwide HIV Cohort have provided clinical data on large numbers of HIV-infected patients. The HIV cohorts in Guinea-Bissau are unique platforms for research and represent real life in many African countries. Poor adherence, lack of HIV viral load measurements, inadequate laboratory facilities, high rates of loss to follow-up, mortality, treatment failure and resistance development, are just some of the challenges faced putting the goal of “90–90–90″ for Guinea-Bissau well out of reach by 2020. Maintaining undetectable viral loads on treatment as a prerequisite of a cure strategy seems not possible at the moment. Thinking beyond one-pill-once-a-day, long-acting antiretroviral treatment options such as injectable drugs or implants may be a better treatment option in settings like Guinea-Bissau and may even pave the way for an HIV cure. If the delivery of antiretroviral treatment in sub-Saharan Africa in a sustainable way for the future should be improved by focusing on existing treatment options or through focusing on new treatment options remains to be determined.

show abstract

Sequence analysis of HIV-1 isolates from Guinea-Bissau: selection of vaccine epitopes relevant in both West African and European countries

Cited by 8 publications

References 52 publications

Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent

Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent

Characterizing novel endogenous retroviruses from genetic variation inferred from short sequence reads

HIV treatment in Guinea-Bissau: room for improvement and time for new treatment options

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