Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques(Macaca leonina)

Northern pig-tailed macaques （NPMs, Macaca leonina） are susceptible to HIV-1 infection largely due to the loss of HIV-l-restricting factor TRIM5a. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences （CDSs） showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection.

HIV-1 can infect northern pig-tailed macaques(Macaca leonina) and form viral reservoirs in vivo

Viral reservoirs of HIV-1 are a major obstacle for curing AIDS. The novel animal models that can be directly infected with HIV-1 will contribute to develop effective strategies for eradicating infections.Here, we inoculated 4 northern pig-tailed macaques(NPM) with the HIV-1 strain HIV-1_(NL4.3) and monitored the infection for approximately 3 years(150 weeks). The HIV-1-infected NPMs showed transient viremia for about 10 weeks after infection. However, cell-associated proviral DNA and viral RNA persisted in the peripheral blood and lymphoid organs for about 3 years. Moreover, replication-competent HIV-1could be successfully recovered from peripheral blood mononuclear cells(PBMCs) during long-term infection. The numbers of resting CD4^+T cells in HIV-1 infected NPMs harboring proviruses fell within a range of 2-to 3-log_(10) per million cells, and these proviruses could be reactivated both ex vivo and in vivo in response to co-stimulation with the latency-reversing agents JQ1 and prostratin. Our results suggested that NPMs can be infected with HIV-1 and a long-term viral reservoir was formed in NPMs,which might serve as a potential model for HIV-1 reservoir research.

Aging induces severe SIV infection accompanied by an increase in follicular CD8+T cells with overactive STAT3 signaling

The number of elderly people living with HIV is increasing globally,and the condition of this population is relatively complicated due to the dual effects of aging and HIV infection.However,the impact of HIV infection combined with aging on the immune homeostasis of secondary lymphoid organs remains unclear.Here,we used the simian immunodeficiency virus mac239(SIVmac239)strain to infect six young and six old Chinese rhesus macaques(ChRMs)and compared the infection characteristics of the two groups in the chronic stage through multiplex immunofluorescence staining of lymph nodes.The results showed that the SIV production and CD4/CD8 ratio inversion in old ChRMs were more severe than those in young ChRMs in both the peripheral blood and the lymph nodes,especially when a large number of CD8+T cells infiltrated the follicles and germinal centers.STAT3 in these follicular CXCR5+CD8+T cells was highly activated,with high expression of granzyme B,which might be caused by the severe inflammatory milieu in the follicles of old ChRMs.This study indicates that aging may be a cofactor involved in SIV-induced immune disorders in secondary lymphoid tissues,affecting the effective antiviral activity of highly enriched follicular CXCR5+CD8+cells.