Phenotypic analysis was performed on 13 HIV-1 strains isolated between 2000 and 2001. Syncytium-inducing and non-syncytium-inducing subtype C viruses were found, most of which used more than one co-receptor. For the first time subtype B viruses were isolated from South African heterosexual patients, a subtype previously associated only with homosexual spread in this geographical region.

The objective of the study was to assess the genotypic and phenotypic properties of 18 viral strains from human immunodeficiency virus-1 (HIV-1) positive patients and to identify subtype C isolates for vaccine design strategies. All the isolates were non-syncytium-inducing (NSI) in both the primary and MT-2 cell cultures. The amino acid charge of the V3 loop correlated with the NSI phenotype of the strains. The V3 competitive peptide enzyme immunoassay and DNA sequencing of the partial gp120 region gave concordant results on the 15 subtype C strains, whereas the three B genotypes gave a positive to B, a nonreactive to B, and a dual reaction to the B-D peptides, respectively. Sixteen of the isolates used only CCR5 as coreceptor whereas two isolates made use of additional coreceptors including CXCR4. In summary, all our subtype C isolates are NSI phenotypically and almost all of them use CCR5 exclusively as their coreceptor.

Background: To investigate the possible role of FHIT, a possible tumour suppressor gene, in oral carcinogenesis, we examined 17 oral squamous cell carcinomas (OSCCs) for genetic alterations. Materials and Methods: Fresh tissue was obtained during surgery, snap frozen in liquid nitrogen and stored at -70 degreesC. Nested PCR amplification to examine the integrity of FHIT mRNA was performed on the reverse transcribed complementary DNA obtained from the frozen normal and tumour tissue. Immunohistochemistry was done on formal in-fixed paraffin-embedded tissue protein from the same cases using a polyclonal antiserum against the full length Fhit. Results: Twelve out 17 (71%) OSCCs showed reduced or absent Fhit protein and half of the cases with reduced Fhit protein exhibited aberrant RT-PCR products. Conclusion: Immunohistochemical detection of Fhit protein expression in OSCCs is the more sensitive method to determine the status of Fhit in these tumours, in agreement with previous studies of other tumour types.

HIV infection in children is mainly acquired through vertical transmission from an infected mother. We report epidemiological and molecular evidence of horizontal transmission between two siblings. This is, to our knowledge, the first documented case from Africa, where socioeconomic conditions may be more conducive to horizontal spread than in industrialized countries. In 1996, a 3½-year-old HIV-infected child (child A), with HIV-negative parents, was referred to our infectious diseases clinic. He initially presented with generalized lymphadenopathy, hepatosplenomegaly and cryptosporidial diarrhoea. We confirmed HIV infection by enzyme immunosorbent assay (ELISA) antibody detection and reverse transcriptase–polymerase chain reaction (RT–PCR) for HIV RNA detection. HIV negativity in the parents and sibling (child B) were also confirmed. Child A had an uncomplicated normal birth and was breastfed by his mother for 4 months (surrogate breastfeeding was denied). He had been hospitalized at 3 years of age for diarrhoea and acute bacterial meningitis, and had never received a blood transfusion. Seventeen months later, the sibling (child B), 28 months younger than his brother, presented with conjunctivitis and chronic otorrhoea. Cervical lymphadenopathy and hepatomegaly were noted. He was retested for HIV (ELISA and RT–PCR) and was found to be infected. Medical records disclosed an episode of gastroenteritis and herpes stomatitis 13 months earlier. Both parents remained negative by ELISA and RT–PCR. HLA genotyping confirmed the genetic lineage between the children and their parents with 99.9% certainty. The two brothers and their parents lived alone in the same household. There was no history or clinical evidence of sexual abuse. They were never immunized on the same day and the clinics do not re-use needles or syringes. In the period between child B's negative and positive serology, child A, who shared a bed with his sibling, had a few episodes of epistaxis, staining the pillow. Child B was also exposed to the purulent otorrhoea of child A, including during the period when child B had herpes stomatitis. Phylogenetic analysis was performed on a 337 base pair region of the env gene, including the V3 domain of the viral strains from the two brothers. Distance calculation, tree construction methods and bootstrap analysis were performed using clustal W. The two strains differed by 3.2%, indicating horizontal transmission from child A to child B (Fig. 1). Contact with blood from epistaxis or purulent otorrhoea are implicated as a means of transmission. Child B's episode of herpes stomatitis may have contributed by compromising the mucosal integrity. Leitner et al. [1] evaluated the use of phylogenetic methods in their study of HIV transmission patterns and found these methods to be very accurate. A few sporadic cases of horizontal transmission in the household involving children have been reported from the USA and Europe. In two of those cases molecular evidence supported horizontal transmission [2,3]. Epidemiological evidence indicated mucocutaneous exposure to infected blood.Fig. 1.: Phylogenetic tree analysis of children A and B HIV-1 sequences and Los Alamos HIV database reference sequences (A-SF1703, B-HXB2, B-RF, C-ZAM18, C-92BR025.8, C-ETH2220, C-UG268, D-ELI, E-90CR402.1, E-93TH253.3, F-BZ126A, F-BZ163A, G-92RU131.9, G-92UG975.10, H-CA13, H-V1557, O-ANT70). An indication of the degree of sequence dissimilarity is shown on the horizontal axis.Only one study from Africa (Zaire) has investigated the possibility of household transmission. Mann and colleagues [4] surveyed 204 household contacts of 46 AIDS patients and 155 of 43 seronegative controls. Although the authors’ conclusion negated horizontal transmission, their statistical methodology was questioned and on re-analysis the risk was thought to be real [5]. Razel [5] estimated the risk of HIV infection through household contact to be 0.4 transmissions per 100 person-years of contact. The origin of child A's infection still remains an open question because both parents were seronegative. Since the start of our investigation two other HIV-infected children, with unknown sources of infection (parents also HIV negative), were detected at the same regional hospital. These children all come from poor socioeconomic backgrounds where overcrowding is conducive to skin or mucous membrane contact with HIV-infected blood and other secretions. In conclusion, we have documented the possible horizontal spread of HIV between two siblings, supported by phylogenetic analysis, and have begun additional studies of this form of transmission. Heidi Ortha Susan Engelbrechta Mark F. Cottonb Brenda A. Robsona Tracey-Lee Smitha H. Simon Schaafb Beryl Leibrandtc Els Dobbelsc Estrelita Janse van Rensburga

AIDS Research and Human RetrovirusesVol. 15, No. 1 Subtyping of Human T Cell Lymphotropic Virus Type I from Tropical Spastic Paraparesis/HTLV-Associated Myelopathy Patients in MozambiqueSusan Engelbrecht, Irene Koulinska, Tracey-Lee Smith, Brenda A. Robson, Jorge Barreto, and Estrelita J. Van RensburgSusan EngelbrechtSearch for more papers by this author, Irene KoulinskaSearch for more papers by this author, Tracey-Lee SmithSearch for more papers by this author, Brenda A. RobsonSearch for more papers by this author, Jorge BarretoSearch for more papers by this author, and Estrelita J. Van RensburgSearch for more papers by this authorPublished Online:5 Jul 2004https://doi.org/10.1089/088922299311736AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Subtyping of Human T Cell Lymphotropic Virus Type I from Tropical Spastic Paraparesis/HTLV-Associated Myelopathy Patients in Mozambique." , 15(1), pp. 71–72FiguresReferencesRelatedDetailsCited ByHuman T-Lymphotropic Virus Type 1 Infection in a Patient with Arthritis in Mozambique: Molecular Characterization of Human T-Lymphotropic Virus Type 1 Isolate Adele Caterino-de-Araujo, Mariana Cavalheiro Magri, Emanuela Avelar Silva Costa, and Rolanda Carmen Rafael Manuel29 November 2011 | AIDS Research and Human Retroviruses, Vol. 27, No. 12Genetic Characterization of Human T-Cell Lymphotropic Virus Type 1 in Mozambique: Transcontinental Lineages Drive the HTLV-1 Endemic12 April 2011 | PLoS Neglected Tropical Diseases, Vol. 5, No. 4Prevalence of Human T-Cell Lymphotropic Virus (HTLV-1/2) in Individuals from Public Health Centers in Mozambique Adele Caterino-de-Araujo, Mariana Cavalheiro Magri, Emanuela Avelar Silva Costa, and Rolanda Carmen Rafael Manuel17 May 2010 | AIDS Research and Human Retroviruses, Vol. 26, No. 5Serologic and molecular typing of human T-lymphotropic virus among blood donors in Maputo City, MozambiqueTransfusion, Vol. 49, No. 6Phylogeny of Human T Cell Lymphotropic Virus Type 1 in Peru: A High Degree of Evolutionary Relatedness with South African Isolates Gianguglielmo Zehender, Erika Ebranati, Flavia Bernini, Chiara De Maddalena, Camilla Giambelli, Jaime Collins, Ada Valverde, Zeffirino Montin, and Massimo Galli6 October 2007 | AIDS Research and Human Retroviruses, Vol. 23, No. 9HIV and HTLV Prevalences Among Women Seen for Sexually Transmitted Diseases or Pregnancy Follow-Up in Maputo, MozambiqueJournal of Acquired Immune Deficiency Syndromes, Vol. 23, No. 2HIV and HTLV Prevalences Among Women Seen for Sexually Transmitted Diseases or Pregnancy Follow-Up in Maputo, MozambiqueJAIDS Journal of Acquired Immune Deficiency Syndromes, Vol. 23, No. 2 Volume 15Issue 1Jan 1999 To cite this article:Susan Engelbrecht, Irene Koulinska, Tracey-Lee Smith, Brenda A. Robson, Jorge Barreto, and Estrelita J. Van Rensburg.Subtyping of Human T Cell Lymphotropic Virus Type I from Tropical Spastic Paraparesis/HTLV-Associated Myelopathy Patients in Mozambique.AIDS Research and Human Retroviruses.Jan 1999.71-72.http://doi.org/10.1089/088922299311736Published in Volume: 15 Issue 1: July 5, 2004PDF download

More than 20.8 million people are living with HIV/AIDS in sub-Saharan Africa, with southern Africa the worst affected area and accounting for one of the fastest growing AIDS epidemics worldwide. Samples from 81 patients, including 25 from KwaZulu-Natal, 26 from Gauteng, 5 from Mpumalanga, and 25 from Western Cape Province, were serotyped using a competitive V3 peptide enzyme immunoassay (cPEIA). Viral RNA was also isolated from serum and the V3 region amplified by reverse transcriptase polymerase chain reaction (RTPCR) to obtain a 240-bp product for direct sequencing of 29 samples. CLUSTAL W was used to make multiple sequence alignments. Distance calculation, tree construction methods, and bootstrap analysis were done using TREECON. Subtype C-like V3 loop sequences predominate in all provinces tested in South Africa. Discordant sero- and genotype results were observed in one patient only. The correlation between sero- and genotyping was 96% (24 of 25) in KwaZulu-Natal and 100% in Gauteng and Mpumalanga. In Western Cape Province 18% of patients were identified as sero/genotype B and 82% as sero/genotype C. Our data show that results of the second-generation V3 cPEIA correlated well with V3 sequencing and would be a rapid and affordable screening test to monitor the explosive southern African HIV-1 epidemic.

More than 20.8 million people are infected with HIV in sub-Saharan Africa, with South Africa having one of the fastest growing HIV-1 epidemics, where an estimated 2.4 million people were infected. Thirty-two sera from 25 patients were tested for their ability to neutralize HTLV-IIIB (IIIB) and four primary isolates representing subtypes B, C, D, and a recombinant gag C/env B type. A CEM-SS cell line-based assay was used and the neutralizing titer was defined as the reciprocal of the highest dilution giving a 50% reduction in p24 antigen production. All isolates were neutralized better by subtype-specific sera, except for the C4714 strain, which was neutralized by both subtype B and C sera. C4714 was neutralized by 18/25 (72%) sera, IIIB by 19/32 (59%) sera, D482 by 7/31(23%) sera, B3245 by 6/29 (21%) sera, and the recombinant B/C1491 isolate by 4/25 (16%) sera. Five sera were unable to neutralize any of the isolates. The V3 region of the isolates used in the neutralization assay was amplified by PCR, directly sequenced, and analyzed to reveal variability between the consensus HIV-1 sequences and the isolates. HIV-1 strain C4714 was neutralized more effectively with the sera tested than the IIIIB laboratory strain. Variability in the amino acid sequence of the V3 region, which can alter the conformation of the V3 loop secondary structure, can influence the neutralization of a particular viral isolate. Vaccine formulations should be broadened to include multiple subtypes, especially C subtypes, which is rapidly spreading worldwide.

This article was co-written by Prof Janse van Rensburg before she joined the University of Pretoria.

AIDS Research and Human RetrovirusesVol. 14, No. 11 Sequence Note: HIV Type 1 V3 Region Subtyping in KwaZulu-Natal, a High-Seroprevalence South African RegionDAYA MOODLEY, TRACEY-LEE SMITH, ESTRELITA J. VAN RENSBURG, JACK MOODLEY, and SUSAN ENGELBRECHTDAYA MOODLEYSearch for more papers by this author, TRACEY-LEE SMITHSearch for more papers by this author, ESTRELITA J. VAN RENSBURGSearch for more papers by this author, JACK MOODLEYSearch for more papers by this author, and SUSAN ENGELBRECHTSearch for more papers by this authorPublished Online:15 Mar 2009https://doi.org/10.1089/aid.1998.14.1015AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byThe Reverse Transcriptase 67N 70R 215Y Genotype Is the Predominant TAM Pathway Associated with Virologic Failure among HIV Type 1C-Infected Adults Treated with ZDV/ddI-Containing HAART in Southern Africa Vlad Novitsky, C. William Wester, Victor DeGruttola, Hermann Bussmann, Simani Gaseitsiwe, Ann Thomas, Sikhulile Moyo, Rosemary Musonda, Erik Van Widenfelt, Richard G. Marlink, and M. Essex3 August 2007 | AIDS Research and Human Retroviruses, Vol. 23, No. 7Genotypic and phenotypic analysis of theenv gene from South African HIV-1 subtype B and C isolates12 August 2002 | Journal of Medical Virology, Vol. 68, No. 2Rapid Characterization of HIV Clade C-Specific Cytotoxic T Lymphocyte Responses in Infected African Children and Adults25 January 2006 | Annals of the New York Academy of Sciences, Vol. 918, No. 1Differential Narrow Focusing of Immunodominant Human Immunodeficiency Virus Gag-Specific Cytotoxic T-Lymphocyte Responses in Infected African and Caucasoid Adults and ChildrenJournal of Virology, Vol. 74, No. 12HIV Type 1 V3 Domain Serotyping and Genotyping in Gauteng, Mpumalanga, KwaZulu-Natal, and Western Cape Provinces of South Africa S. Engelbrecht, T.-L. Smith, P. Kasper, E. Faatz, M. Zeier, D. Moodley, C.G. Clay, and E.J. Van Rensburg5 July 2004 | AIDS Research and Human Retroviruses, Vol. 15, No. 4A Predominantly HIV Type 1 Subtype C-Restricted Epidemic in South African Urban Populations J.H. Van Harmelen, E. Van Der Ryst, A.S. Loubser, D. York, S. Madurai, S. Lyons, R. Wood, and C. Williamson5 July 2004 | AIDS Research and Human Retroviruses, Vol. 15, No. 4 Volume 14Issue 11Jul 1998 To cite this article:DAYA MOODLEY, TRACEY-LEE SMITH, ESTRELITA J. VAN RENSBURG, JACK MOODLEY, and SUSAN ENGELBRECHT.Sequence Note: HIV Type 1 V3 Region Subtyping in KwaZulu-Natal, a High-Seroprevalence South African Region.AIDS Research and Human Retroviruses.Jul 1998.1015-1018.http://doi.org/10.1089/aid.1998.14.1015Published in Volume: 14 Issue 11: March 15, 2009PDF download

AIDS Research and Human RetrovirusesVol. 11, No. 10 Identification of env Subtypes in Fourteen HIV Type 1 Isolates from South AfricaSUSAN ENGELBRECHT, JANETTA D. LATEN, TRACEY-LEE SMITH, and ESTRELITA J. van RENSBURGSUSAN ENGELBRECHT, JANETTA D. LATEN, TRACEY-LEE SMITH, and ESTRELITA J. van RENSBURGPublished Online:16 Mar 2009https://doi.org/10.1089/aid.1995.11.1269AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited ByNear full-length HIV-1 subtype B sequences from the early South African epidemic, detecting a BD unique recombinant form (URF) from a sample in 198517 April 2019 | Scientific Reports, Vol. 9, No. 1HIV-1 diversity in an antiretroviral treatment naïve cohort from Bushbuckridge, Mpumalanga Province, South Africa13 February 2015 | Virology Journal, Vol. 12, No. 1Identification and Genetic Characterization of Unique HIV-1 A1/C Recombinant Strain in South Africa Andrew M. Musyoki, Johnny N. Rakgole, Gloria Selabe, and Jeffrey Mphahlele17 December 2014 | AIDS Research and Human Retroviruses, Vol. 31, No. 3HIV-1 Subtypes B and C Unique Recombinant Forms (URFs) and Transmitted Drug Resistance Identified in the Western Cape Province, South Africa7 March 2014 | PLoS ONE, Vol. 9, No. 3HIV-1 subtype C is not associated with higher risk of heterosexual HIV-1 transmissionAIDS, Vol. 28, No. 2Construction of a High Titer Infectious HIV-1 Subtype C Proviral Clone from South Africa24 September 2012 | Viruses, Vol. 4, No. 9Emergence and diversity of different HIV-1 subtypes in South Africa, 2000-2001Journal of Medical Virology, Vol. 81, No. 11Southern Africa (South Africa, Botswana, Lesotho, Malawi, Mozambique, Namibia, Swaziland, Zambia, Zimbabwe)Complete Genome Sequencing of a Non-syncytium-Inducing HIV Type 1 Subtype D Strain from Cape Town, South Africa Graeme B. Jacobs, André G. Loxton, Annette Laten, and Susan Engelbrecht26 December 2007 | AIDS Research and Human Retroviruses, Vol. 23, No. 12Serotyping and genotyping of HIV-1 infection in residents of Khayelitsha, Cape Town, South Africa1 January 2006 | Journal of Medical Virology, Vol. 78, No. 12Sequence Analysis of Near Full-Length HIV Type 1 Subtype D Primary Strains Isolated in Cape Town, South Africa, from 1984 to 1986 André G. Loxton, Florette Treurnicht, Annette Laten, Estrelita Janse Van Rensburg, and Susan Engelbrecht1 June 2005 | AIDS Research and Human Retroviruses, Vol. 21, No. 5Characterization of Human Immunodeficiency Virus Type 1 from a Previously Unexplored Region of South Africa with a High HIV Prevalence Pascal Obong Bessong, Chikwelu Larry Obi, Tonie Cilliers, Isaac Choge, Mary Phoswa, Candice Pillay, Maria Papathanasopoulos, and Lynn Morris21 January 2005 | AIDS Research and Human Retroviruses, Vol. 21, No. 1Genotypic and phenotypic analysis of theenv gene from South African HIV-1 subtype B and C isolates12 August 2002 | Journal of Medical Virology, Vol. 68, No. 2HIV-1 Subtype A, D, G, AG and Unclassified Sequences Identified in South Africa Helba Bredell, Gillian Hunt, Alison Casteling, Tonie Cilliers, Celia Rademeyer, Mia Coetzer, Steven Miller, David Johnson, Caroline T. Tiemessen, Desmond J. Martin, Carolyn Williamson, and Lynn Morris5 July 2004 | AIDS Research and Human Retroviruses, Vol. 18, No. 9Genetic Analysis of the Complete gag and env Genes of HIV Type 1 Subtype C Primary Isolates from South Africa Susan Engelbrecht, Tania de Villiers, Candice C. Sampson, Jan zur Megede, Susan W. Barnett, and Estrelita Janse van Rensburg5 July 2004 | AIDS Research and Human Retroviruses, Vol. 17, No. 16HIV Type 1 V3 Domain Serotyping and Genotyping in Gauteng, Mpumalanga, KwaZulu-Natal, and Western Cape Provinces of South Africa S. Engelbrecht, T.-L. Smith, P. Kasper, E. Faatz, M. Zeier, D. Moodley, C.G. Clay, and E.J. Van Rensburg5 July 2004 | AIDS Research and Human Retroviruses, Vol. 15, No. 4Restriction fragment length polymorphism analysis for rapid gag subtype determination of human immunodeficiency virus Type 1 in South AfricaJournal of Virological Methods, Vol. 78, No. 1-2Neutralization of HIV-1 subtypes: Implications for vaccine formulationsJournal of Medical Virology, Vol. 56, No. 3Molecular Epidemiology of HIV-1 in Brazil: High Prevalence of HIV-1 Subtype B and Identification of an HIV-1 Subtype D Infection in the City of Rio de Janeiro, BrazilJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 18, No. 5Sequence Note: HIV Type 1 V3 Region Subtyping in KwaZulu-Natal, a High-Seroprevalence South African Region DAYA MOODLEY, TRACEY-LEE SMITH, ESTRELITA J. VAN RENSBURG, JACK MOODLEY, and SUSAN ENGELBRECHT15 March 2009 | AIDS Research and Human Retroviruses, Vol. 14, No. 11Sequence Note: Variation in HIV Type 1 V3 Region env Sequences from Mozambique SUSAN ENGELBRECHT, IRENE KOULINSKA, TRACEY-LEE SMITH, JORGE BARRETO, and ESTRELITA J. VAN RENSBURG15 March 2009 | AIDS Research and Human Retroviruses, Vol. 14, No. 9Genetic Characterization of HIV Type 1 from Migrant Workers in Three South African Gold Mines HELBA BREDELL, CAROLYN WILLIAMSON, PAMELA SONNENBERG, DESMOND J. MARTIN, and LYNN MORRIS15 March 2009 | AIDS Research and Human Retroviruses, Vol. 14, No. 8An association between HIV-1 subtypes and mode of transmission in Cape Town, South AfricaAIDS, Vol. 11, No. 1HIV-1 Subtypes and Recombinants Volume 11Issue 10Oct 1995 To cite this article:SUSAN ENGELBRECHT, JANETTA D. LATEN, TRACEY-LEE SMITH, and ESTRELITA J. van RENSBURG.Identification of env Subtypes in Fourteen HIV Type 1 Isolates from South Africa.AIDS Research and Human Retroviruses.Oct 1995.1269-1271.http://doi.org/10.1089/aid.1995.11.1269Published in Volume: 11 Issue 10: March 16, 2009PDF download