Abstract
A significant portion of the world’s population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2), that cause a wide range of diseases including genital herpes, oro-facial herpes, and the potentially blinding ocular herpes. While the global prevalence and distribution of HSV-1 and HSV-2 infections cannot be exactly established, the general trends indicate that: (i) HSV-1 infections are much more prevalent globally than HSV-2; (ii) over a half billion people worldwide are infected with HSV-2; (iii) the sub-Saharan African populations account for a disproportionate burden of genital herpes infections and diseases; (iv) the dramatic differences in the prevalence of herpes infections between regions of the world appear to be associated with differences in the frequencies of human leukocyte antigen (HLA) alleles. The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations. Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A∗24, HLA-B∗27, HLA-B∗53 and HLA-B∗58 alleles. In contrast, low prevalence of herpes infection and disease appears to be associated with high frequency of HLA-B∗44 allele. The finding will aid in developing a T-cell epitope-based universal herpes vaccine and immunotherapy.
Highlights
A significant portion of the world’s population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2) [1,2,3]
In order to disentangle the respective contribution of the human leukocyte antigen (HLA)-A, HLA-B and HLA-C alleles in HSV-1 and HSV-2 infections: (1) We performed a systematic haplotypic analysis in the four major world’s populations (Caucasoids, Orientals, Hispanics and Blacks), which display various prevalence of HSV-1 and HSV-2 infection; (2) PubMed® (1966-present) was used to identify cross-sectional studies with HSV-1 and HSV-2 sero-prevalence data and to identify the highest HLA class I allele that are specific to distinct populations with low vs. high prevalence of HSV-1 and HSV-2 infections; (3) The potential association of the HLA class I alleles [35,36,37] with high vs. low prevalence of herpes infections was determined
HLA-B*44 high expression and frequency that appears to positively correlate with low prevalence of HSV-2 infection known in Caucasoid European population (Fig. 2), makes HLA-B*44-restricted epitopes “good” candidates to be included in future herpes vaccine, and ; (3) to exclude the “symptomatic” epitopes that are associated with HLA-A, HLA-B, and HLA-C alleles most represented in endemic areas, because those HLA-A, HLA-B, and HLA-C alleles and associated epitopes might be involved in susceptibility to HSV infection and may facilitate progression to herpetic disease
Summary
A significant portion of the world’s population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2) [1,2,3]. While the exact estimates of HSV-1 and HSV-2 prevalence in the world are limited by poor availability of sero-epidemiological data, general trends indicate that HSV-2 infections continue to spread globally: (i) HSV-2 affects over 540 million people, aged 14-49 years, worldwide, with an estimate of 23.6 million people newly infected per year [1,2,3,4]; (ii) In the United States, about one in six individuals from the sexually active population (i.e. between 14 and 49 years of age) are infected with HSV-2, which is equivalent to approximately 60 million people, with the highest prevalence among non-Hispanic black individuals and the lowest among those of Asian descent; (iii) globally, more women are infected by HSV-2 than men [4, 5]; (iv) the number of infected men and women increases with age [4]; (v) the prevalence of herpes infection varies substantially by region, it is mostly higher in developing than in developed regions; (vi) HSV-2 and HSV-1 prevalence varies markedly by country, by region within country, and by population subgroup [6]; (vii) globally, genital herpes caused by HSV-2 is frequent in sub-Saharan Africa, countries form Latin America, and South East Asia, with greater than 20% of the populations in the sub-regions suffering from genital herpes infection [6].
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