Spatial technologies to evaluate the HIV-1 reservoir and its microenvironment in the lymph node.

The presence of the HIV-1 reservoir, a group of immune cells that contain intact, integrated, and replication-competent proviruses, is a major challenge to cure HIV-1. HIV-1 reservoir cells are largely unaffected by the cytopathic effects of viruses, antiviral immune responses, or antiretroviral therapy (ART). The HIV-1 reservoir is seeded early during HIV-1 infection and augmented during active viral replication. CD4+ T cells are the primary target for HIV-1 infection, and recent studies suggest that memory T follicular helper cells within the lymph node, more precisely in the B cell follicle, harbor integrated provirus, which contribute to viral rebound upon ART discontinuation. The B cell follicle, more specifically the germinal center, possesses a unique environment because of its distinct property of being partly immune privileged, potentially allowing HIV-1-infected cells within the lymph nodes to be protected from CD8+ T cells. This modified immune response in the germinal center of the follicle is potentially explained by the exclusion of CD8+ T cells and the presence of T regulatory cells at the junction of the follicle and extrafollicular region. The proviral makeup of HIV-1-infected cells is similar in lymph nodes and blood, suggesting trafficking between these compartments. Little is known about the cell-to-cell interactions, microenvironment of HIV-1-infected cells in the follicle, and trafficking between the lymph node follicle and other body compartments. Applying a spatiotemporal approach that integrates genomics, transcriptomics, and proteomics to investigate the HIV-1 reservoir and its neighboring cells in the lymph node has promising potential for informing HIV-1 cure efforts.

Hepatitis B Virus in People who Inject Drugs and Men who Have Sex With Men With HIV in India: A Cross-sectional Study.

Background: People with HIV (PWH) who are coinfected with hepatitis B virus (HBV) have a higher risk of mortality compared with PWH alone. Populations such as people who inject drugs (PWID) and men who have sex with men (MSM) are particularly at high risk for HBV acquisition; yet, limited epidemiological data from these populations exist on HBV prevalence from low- and middle-income country settings (LMICs). Methods: We characterized the prevalence and correlates of HBV serological markers in a sample of PWID and MSM with HIV recruited across 15 Indian cities using hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs). Testing of stored specimens for the presence of these markers was performed on the Abbott ARCHITECT i1000 as per the manufacturer's instructions. Correlates of ever being infected with HBV (reactive for anti-HBc and/or HBsAg) and chronic HBV (reactive for HBsAg) among those ever infected were assessed using univariable and multivariable multilevel logistic regression models accounting for site-level clustering. Results: A total of 2198 (95%) of the 2314 participants recruited for the trial were screened for HBV markers. The median age among the PWID and MSM participants was 30 and 32 years, respectively. The prevalence of ever being infected with HBV was 75.6% vs 46.9% in PWID vs MSM, respectively (P < .01); prevalence of chronic infection was also higher in PWID vs MSM (14.1% vs 9.5%; P < .01). Correlates of ever being infected with HBV among PWID included unstable housing (adjusted odds ratio [aOR], 5.02) and sharing injection paraphernalia (aOR, 2.70), and among MSM, correlates included history of injection drug use (aOR, 4.87) and gender identity. The prevalence of isolated core (anti-HBc in the absence of anti-HBs) was 34.7% vs 29.4% in PWID vs MSM (P < .05). Vaccination serostatus was <10% in both populations. Conclusions: In this large sample of PWID and MSM with HIV, we observed a high prevalence of serology consistent with HBV infection and low vaccination, highlighting the need for routine screening and catch-up vaccination. The high prevalence of isolated anti-HBc reactivity highlights the need to understand the risk of reactivation with this serological pattern.

Hepatitis B virus DNA and RNA persist in liver after serologic recovery in persons with hepatitis C virus.

After recovery from a hepatitis B virus (HBV) infection, reactivation can occur with immunosuppression; thus, it is assumed that replication competent HBV persists in the liver. We sought to detect persistent HBV from 13 people with spontaneous recovery. We quantified HBV DNA and RNA in core liver biopsies (median 1.72x106 cells) from people who inject drugs (PWID). Among 13 biopsies, 8 (61%) had evidence of HBV DNA or RNA and 5 (38%) had both HBV DNA and RNA. mRNAs derived from cccDNA and integrated HBV DNA. Here, we show prevalent HBV DNA and RNA despite clinical recovery in PWID.

We used a sensitive method to determine the amount of hepatitis B virus DNA or RNA in the livers of 13 individuals who recovered from hepatitis B virus infection. We found viral DNA or RNA in the liver in 61% of individuals despite no detectable virus in blood. Our findings support that eliminating all hepatitis B from the liver is a difficult treatment goal.

Intracellular Host Restriction of Hepatitis B Virus Replication.

The hepatitis B virus (HBV) infects hepatocytes and hijacks host cellular mechanisms for its replication. Host proteins can be frontline effectors of the cell's defense and restrict viral replication by impeding multiple steps during its intracellular lifecycle. This review summarizes many of the well-described restriction factors, their mechanisms of restriction, and counteractive measures of HBV, with a special focus on viral transcription. We discuss some of the limitations and knowledge gaps about the restriction factors, highlighting how these factors may be harnessed to facilitate therapeutic strategies against HBV.