Nosik Marina, Berezhnya Elena, Bystritskaya Elizaveta, Kiseleva Irina, Lobach Olga, Kireev Dmitry, Svitich Oxana
I.I. Mechnikov Institute of Vaccines and Sera, 105064 Moscow, Russia.
Central Research Institute of Epidemiology, 111123 Moscow, Russia.
Pathogens. 2023 Jun 27;12(7):880. doi: 10.3390/pathogens12070880.
More than 50% of all people living with HIV worldwide are women. Globally, HIV/AIDS is the leading cause of death among women aged 15 to 44. The safe and effective methods of hormonal contraception are an essential component of preventive medical care in order to reduce maternal and infant mortality. However, there is limited knowledge regarding the effect of hormones on the rate of viral replication in HIV infection, especially non-B subtypes. The goal of the present work was to study in vitro how the female hormones β-estradiol and progesterone affect the replication of the HIV-1 subtypes A6, CRF02_AG, and B. The findings show that high doses of hormones enhanced the replication of HIV-1 sub-subtype A6 by an average of 1.75 times and the recombinant variant CRF02_AG by 1.4 times but did not affect the replication of HIV-1 subtype B. No difference was detected in the expression of CCR5 and CXCR4 co-receptors on the cell surface, either in the presence or absence of hormones. However, one of the reasons for the increased viral replication could be the modulated TLRs secretion, as it was found that high doses of estradiol and progesterone upregulated, to varying degrees, the expression of TLR2 and TLR9 genes in the PBMCs of female donors infected with HIV-1 sub-subtype A6.
全球感染艾滋病毒的人群中，超过50%为女性。在全球范围内，艾滋病毒/艾滋病是15至44岁女性死亡的主要原因。安全有效的激素避孕方法是预防性医疗保健的重要组成部分，以降低孕产妇和婴儿死亡率。然而，关于激素对艾滋病毒感染中病毒复制率的影响，尤其是非B亚型，人们了解有限。本研究的目的是在体外研究女性激素β-雌二醇和孕酮如何影响HIV-1 A6亚型、CRF02_AG重组亚型和B亚型的复制。研究结果表明，高剂量激素使HIV-1 A6亚亚型的复制平均增强了1.75倍，使重组变体CRF02_AG的复制增强了1.4倍，但对HIV-1 B亚型的复制没有影响。无论有无激素，细胞表面CCR5和CXCR4共受体的表达均未检测到差异。然而，病毒复制增加的原因之一可能是Toll样受体（TLR）分泌的调节，因为发现高剂量的雌二醇和孕酮不同程度地上调了感染HIV-1 A6亚亚型的女性供体外周血单核细胞（PBMC）中TLR2和TLR9基因的表达。
