HIV-1 Infection Alters the Viral Composition of Plasma in Men Who Have Sex with Men

Abstract

Altered gut virome and expanded abundance of certain viruses were found in HIV-1-infected individuals. It remains largely unknown how plasma virus composition changes during HIV-1 infection and antiretroviral therapy (ART). We performed viral metagenomic analysis on viral particles enriched from human plasma from 101 men who have sex with men (MSM) with or without HIV-1 infection and whether or not on ART and compared the differences in the plasma virome. An increased plasma viral abundance of main eukaryotic viruses was observed during HIV-1 infection in MSM, especially in AIDS patients (CD4+ T cell counts of <200). Anellovirus, pegivirus and hepatitis B virus (HBV) were the most abundant blood-borne viruses detected among MSM and HIV-1-infected individuals, and anellovirus and pegivirus were closely related to HIV-1 infection. High diversity of anelloviruses was found mostly in HIV-1-infected MSM, and their abundance was positively correlated with the HIV-1 viral load, but negatively correlated with both CD4+ T cell counts and CD4+/CD8+ ratio; in contrast, the abundance of pegivirus showed opposite correlations. ART usage could restore the plasma virome toward that of HIV-1-negative individuals. These data showed an expansion in abundance of certain viruses during HIV-1 infection, indicating the higher risk of shedding some blood-borne viruses in these individuals. These investigations indicate that both anellovirus and pegivirus may play certain roles in HIV disease progression. IMPORTANCE Though an increasing number of studies have indicated the existence of an interaction between the virome and human health or disease, the specific role of these plasma viral components remains largely unsolved. We provide evidence here that an altered plasma virome profile is associated with different immune status of HIV-1 infection. Specific resident viruses, such as anellovirus and pegivirus, may directly or indirectly participate in the disease progression of HIV-1 infection. These results can help to determine their clinical relevance and design potential therapies.

Plasma Virome Reveals Blooms and Transmission of Anellovirus in Intravenous Drug Users with HIV-1, HCV, and/or HBV Infections

“…The infections with HIV-1, HCV and/or HBV may have impaired the immune system, and make the latter unable to control the replication of some resident viruses such as anelloviruses. This is particularly true as some previous studies have consistently found that increased anellovirus load was associated with HIV-1 infections, and the anellovirus load was inversely correlated with CD4 + T cell counts in MSM ( 30 , 56 ).…”

“…The detection rate of HPgV was well consistent with its prevalence in these populations ( 42 ). We previously reported significantly negative correlations of HPgV abundance with HIV-1 and anellovirus abundance in men who have sex with men (MSM) ( 30 ), while the correlations were not found in IDUs ( P = 0.53 and 0.76) (Fig. S5).…”

“…For example, an increased viral burden (e.g., anellovirus and human endogenous retrovirus or HERV) was associated with HIV-1 infection in certain populations ( 28 , 29 ). The altered virome is associated with immune status and disease progression, which raises questions about whether resident plasma viruses could participate in immune response and influence health conditions ( 30 ). Among these resident plasma viruses, anelloviridae is the most abundant and widespread virus family.…”

Early-Life Colonization by Anelloviruses in Infants

“…It is of note, however, that we observed higher AV DNA concentrations in the blood of HIV-1-infected children and the breast milk of HIV-1-positive women compared to samples derived from HIV-1 negative subjects. It has been reported that individuals infected by HIV-1 tend to have higher levels of AV [ 5 , 7 ] and that there is a positive correlation between the levels of immunosuppression and AV abundance [ 28 ]. The HIV-1 positive children from our dataset were not breastfed, but still contained high levels of AVs in their blood already at 2 months of age.…”

“…AVs are widespread in the human population, however, the source and the moment of the first infection are still not clear [ 3 , 4 ]. Of note, higher levels of AV DNA are found in immunocompromised people, for instance, in HIV-1 positive subjects [ 5 , 6 , 7 ]. Since the HIV-1 infected individuals have significantly higher AV DNA prevalence and concentration compared to HIV-1 negative people, the transmission of AVs may be enhanced in these individuals [ 6 ].…”