Impact of HLA-B Allele Variability on HIV-1 Viral Load and CD4+ T Cell Counts

Abstract

Objective: Human Immunodeficiency Virus-1 (HIV-1) has high morbidity and mortality and specifically targets CD4+ T cells, a unique reservoir for HIV-1. CD4+ T cells, which have a role in regulating the immune response and activating other immune cells, recognise HIV-1 antigens presented by Human Leukocyte Antigen (HLA) Class I molecules. HLA-B is most strongly linked to the potential disease outcomes when compared with other HLA classes. It is important to detect HLA-B alleles to determine their effects on HIV-1 infection. By demonstrating the difference in HLA B allele frequency between HIV-1 uninfected and people living with HIV-1 (PLWH), we aimed to demonstrate the correlation between the presence of these alleles in PLWH and the CD4+ T cell count and viral replication levels. Material and Methods: We evaluated the HLA-B allele frequency and its association with HIV-1 infection outcomes in 412 PLWH and 406 healthy individuals. After purification of the genomic DNAs, we identified the HLA-B alleles using PCR-SSP and Luminex technology PCR-SSO methods. Results: We found that the HLA-B*07, *18, *35, *44, and *51 alleles occurred at a frequency greater than 5% in the patient group. In PLWH, the frequency of the HLA-B*57 allele was observed to be lower than that in the control group. The HLA-B*57:01 allele positivity was determined as 1.6%. All patients with HLA-B*57:01 allele positivity had VL <100,000 copies/ml. Patients with the HLA-B*07 and HLA-B*35 alleles exhibited lower CD4+ T cell counts (cells/ mm³) and higher HIV RNA levels (copies/mL). Conclusion: Our findings strongly imply the involvement of other molecular mechanisms, extending beyond the traditional role of class I HLA molecules in antigen presentation. Research into how HLA-B alleles influence HIV-1 infection and disease progression will help us understand who is more susceptible to HIV-1 and how the disease will evolve in different individuals. Further research is essential on this factor, as it holds significant implications for the ongoing, years-long pursuit of an effective HIV vaccine.

Keywords

• HIV-1
• HLA-B
• CD4+T cell
• HLA-B*57:01

HLA-B Alel Değişkenliğinin HIV-1 VİRAL Yük ve CD4+ T Hücre Sayilari Üzerindeki Etkisi

Abstract

Amaç: İnsan immün yetmezlik virüsü-1 (HIV-1) yüksek morbidite ve mortaliteye sahiptir ve özellikle HIV-1 için benzersiz bir rezervuar olan CD4+ T hücrelerini hedef alır. İmmün yanıtı düzenlemede ve diğer immün hücreleri aktive etmede rol oynayan CD4+ T hücreleri, İnsan Lökosit Antijeni (HLA) Sınıf I molekülleri tarafından sunulan HIV-1 antijenlerini tanır. HLA-B, diğer HLA sınıflarıyla karşılaştırıldığında hastalık sonuçlarıyla en güçlü şekilde ilişkilidir. HIV-1 enfeksiyonu üzerindeki etkilerini belirlemek için HLA-B alellerinin varlığını tespit etmek önemlidir. HIV-1 ile enfekte olmayan ve HIV-1 ile yaşayan kişiler (PLWH) arasındaki HLA-B alel sıklığındaki farkı göstererek, bu alellerin PLWH'deki varlığı ve CD4+ T hücre sayısı ile viral replikasyon seviyeleri arasındaki ilişkiyi göstermeyi amaçladık. Gereç ve Yöntemler: 412 PLWH ve 406 sağlıklı bireyde HLA-B alel sıklığını ve HIV-1 enfeksiyon sonuçlarıyla ilişkisini değerlendirdik. Genomik DNA'lar saflaştırıldıktan sonra PCR-SSP ve Luminex teknolojisi PCR-SSO yöntemleri ile HLA-B alellerini tanımladık. Bulgular: HLA-B*07, *18, *35, *44 ve *51 alellerinin hasta grubunda %5'ten daha yüksek bir sıklıkta olduğunu gördük. PLWH'de HLA B*57 alelinin sıklığının kontrol grubuna göre daha düşüktü ve HLA B*57:01 alel pozitifliği %1,6 olarak görüldü. HLA-B*57:01 alel pozitifliği olan tüm hastalarda viral load (VL) <100.000 kopya/ml idi. HLA-B*07 ve HLA-B*35 alellerine sahip hastalar daha düşük CD4+ T hücre sayıları (hücre/mm³) ve daha yüksek HIV RNA seviyeleri (kopya/mL) sergilediler. Sonuç: Bulgularımız antijen sunumunda sınıf I HLA moleküllerinin geleneksel rolünün ötesine uzanan diğer moleküler mekanizmaların dahil olduğunu ima etmektedir. HLA B alellerinin HIV-1 enfeksiyonunu ve hastalık ilerlemesini nasıl etkilediğine dair araştırmalar, kimin HIV-1'e daha duyarlı olduğunu ve hastalığın farklı bireylerde nasıl evrimleşeceğini anlamamıza yardımcı olacaktır. Bu faktör üzerinde daha fazla araştırma yapılması önemlidir çünkü etkili bir HIV aşısının yıllarca süren devam eden arayışı için önemli çıkarımlar taşımaktadır.

Keywords

• HIV-1
• HLA-B
• CD4+ T hücre
• HLA-B*57:01

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