Premature Stop Codon at Residue 101 within HIV-1 Rev Does Not Influence Viral Replication of Clade BC but Severely Reduces Viral Fitness of Clade B

HIV-1 Rev is an accessory protein that plays a key role in nuclear exportation,stabilization,and translation of the viral mRNAs.Rev of HIV-1 clade BC often shows a truncation of 16 AAs due to a premature stop codon at residue 101.This stop codon presents the highest frequency in clade BC and the lowest frequency in clade B.In order to discover the potential biological effect of this truncation on Rev activity and virus replication of clade BC,we constructed Rev expression vectors of clade BC with or without 16 AAs within C-terminal separately,and replaced the stop codon by Q in a CRF07_BC infectious clone.We found that 16 AAs truncation had no effect on expression and activity of Rev in clade BC.Also,the mutation from the stop codon to Q had no effect on virus replication of clade BC.Next,to investigate the effect of this truncation on Rev activity and replication capacity of clade B,Rev expression vectors of clade B carrying or lacking 16 AAs in C-terminal were constructed respectively,and residue Q at position 101 within Rev was substituted by the stop codon in a clade B infectious clone.It was found that 16 AAs truncation significantly down-regulated Rev expression and impaired clade B Rev activity.Furthermore,a Q-to-stop codon substitution within Rev significantly reduced viral replication fitness of clade B.These results indicate that the premature stop codon at residue 101 within Rev exerts diverse impact on viral replication among different HIV-1 clades.

MicroRNA 31 inhibits CD8^(+) T-cell function by increasing its sensitivity to type I interferon signaling in chronic viral infection

Chronic viral infections and malignant tumors can cause T cells to become dysfunctional and exhausted through two different associated immune statuses:inflammation and immunosuppression.Inflammatory immunity is a necessary step for the establishment of the immune response to control infection and cancer.However,once a pathogen cannot be cleared in time or a tumor continues to progress,an immunosuppressive environment involving various immune cells and cytokines may form,thereby promoting the persistence of the pathogen or tumor.Among those immune factors,type I interferons play a dual role by driving inflammation and inducing a variety of suppressive factors that limit immune responses in chronic infection and cancer.

Impact of HIV Pretreatment Drug Resistance on Virological Failure After One-Year Antiretroviral Therapy--China,2018-2019

Summary What is already known about this topic?While antiretroviral therapy(ART)has been rapidly scaled-up among the population living with human immunodeficiency virus or acquired immune deficiency syndrome(HIV/AIDS)patients since 2016,pretreatment drug resistance(PDR)has also increased.