Major Histocompatibility Complex Class II (HLA-DRB and -DQB) Allele Frequencies in Botswana: Association with Human Immunodeficiency Virus Type 1 Infection

ABSTRACT Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Batswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Batswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs.

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Efficient Incorporation of HLA Class II onto Human Immunodeficiency Virus Type 1 Requires Envelope Glycoprotein Packaging

Journal of Virology ◽

10.1128/jvi.74.8.3918-3923.2000 ◽

2000 ◽

Vol 74 (8) ◽

pp. 3918-3923 ◽

Cited By ~ 19

Author(s):

Dexter T. K. Poon ◽

Lori V. Coren ◽

David E. Ott

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Class Ii ◽

Hla Class Ii ◽

Class I ◽

Immunodeficiency Virus ◽

Protein Incorporation ◽

Hiv 1

ABSTRACT HLA class II DR is one of the most abundant cell surface proteins incorporated onto human immunodeficiency virus type 1 (HIV-1) during budding. The mechanism for HLA class II protein incorporation is not known and may involve a viral protein. To determine whether Env affects HLA class II protein incorporation, HIV-1 virions, either with or without Env on their surface, were produced from HLA class II-expressing cells and analyzed by whole-virus immunoprecipitation with antisera against HLA class II proteins. HLA class II proteins were detected on virions only when wild-type Env was incorporated, while similar experiments showed that HLA class I proteins were incorporated independent of Env packaging. Therefore, the packaging of HIV-1 Env protein is required for the efficient incorporation of HLA class II but not class I proteins into the virion. Analysis of two Env mutants revealed that the presence of a 43-amino-acid sequence between amino acids 708 and 750 in the gp41TM cytoplasmic tail was required for efficient incorporation of HLA class II proteins. These data show that HIV-1 actively incorporates HLA class II proteins in a process that, either directly or indirectly, requires Env.

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The Acquisition of Host-Derived Major Histocompatibility Complex Class II Glycoproteins by Human Immunodeficiency Virus Type 1 Accelerates the Process of Virus Entry and Infection in Human T-Lymphoid Cells

Blood ◽

10.1182/blood.v90.3.1091 ◽

1997 ◽

Vol 90 (3) ◽

pp. 1091-1100 ◽

Cited By ~ 56

Author(s):

Réjean Cantin ◽

Jean-François Fortin ◽

Ginette Lamontagne ◽

Michel Tremblay

Keyword(s):

Human Immunodeficiency Virus ◽

T Lymphocytes ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Virus Entry ◽

Class Ii ◽

Mhc Ii ◽

Immunodeficiency Virus ◽

Hiv 1

Abstract Infection by human immunodeficiency virus type 1 (HIV-1) results in a progressive depletion of CD4+ T lymphocytes, leading to fatal immunodeficiency. The mechanisms causing the marked loss of CD4+ T lymphocytes are incompletely understood. However, several lines of evidence indicate that direct cytopathology mediated by HIV-1 is a key element in such CD4+ T-cell depletion. In this study, we investigated whether the previously reported incorporation of host-derived major histocompatibility class II glycoproteins (MHC-II) on HIV-1 can alter its replicative capacity. To achieve this goal, virus stocks were produced in parental MHC-II–expressing RAJI cells and in MHC-II–negative RAJI mutants (RM3), both of which have been stably transfected with human CD4 cDNA to allow productive infection with HIV-1. An enhancement of the rate/efficiency of virus entry was seen after infection with normalized amounts of virions carrying host-derived MHC-II on their surface as compared with inoculation with virions devoid of cellular MHC-II. Data from time-course and infectivity experiments showed that the kinetics of infection were more rapid for virions bearing host-derived MHC-II glycoproteins than for MHC-II–free HIV-1 particles. These results suggest that virally embedded cellular MHC-II glycoproteins are functional and can have a positive effect on early events in the virus replicative cycle. Therefore, we show that the acquisition of cellular MHC-II glycoproteins by HIV-1 can modify its biologic properties and might, consequently, influence the pathogenesis of this retroviral disease.

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The Acquisition of Host-Derived Major Histocompatibility Complex Class II Glycoproteins by Human Immunodeficiency Virus Type 1 Accelerates the Process of Virus Entry and Infection in Human T-Lymphoid Cells

Blood ◽

10.1182/blood.v90.3.1091.1091_1091_1100 ◽

1997 ◽

Vol 90 (3) ◽

pp. 1091-1100 ◽

Cited By ~ 1

Author(s):

Réjean Cantin ◽

Jean-François Fortin ◽

Ginette Lamontagne ◽

Michel Tremblay

Keyword(s):

Human Immunodeficiency Virus ◽

T Lymphocytes ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Virus Entry ◽

Class Ii ◽

Mhc Ii ◽

Immunodeficiency Virus ◽

Hiv 1

Infection by human immunodeficiency virus type 1 (HIV-1) results in a progressive depletion of CD4+ T lymphocytes, leading to fatal immunodeficiency. The mechanisms causing the marked loss of CD4+ T lymphocytes are incompletely understood. However, several lines of evidence indicate that direct cytopathology mediated by HIV-1 is a key element in such CD4+ T-cell depletion. In this study, we investigated whether the previously reported incorporation of host-derived major histocompatibility class II glycoproteins (MHC-II) on HIV-1 can alter its replicative capacity. To achieve this goal, virus stocks were produced in parental MHC-II–expressing RAJI cells and in MHC-II–negative RAJI mutants (RM3), both of which have been stably transfected with human CD4 cDNA to allow productive infection with HIV-1. An enhancement of the rate/efficiency of virus entry was seen after infection with normalized amounts of virions carrying host-derived MHC-II on their surface as compared with inoculation with virions devoid of cellular MHC-II. Data from time-course and infectivity experiments showed that the kinetics of infection were more rapid for virions bearing host-derived MHC-II glycoproteins than for MHC-II–free HIV-1 particles. These results suggest that virally embedded cellular MHC-II glycoproteins are functional and can have a positive effect on early events in the virus replicative cycle. Therefore, we show that the acquisition of cellular MHC-II glycoproteins by HIV-1 can modify its biologic properties and might, consequently, influence the pathogenesis of this retroviral disease.

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