SUMMARY: A major impediment for HIV cure is the ability of the virus to integrate its genome in the form of replication-competent proviral DNA into the cellular genome of the host and remain transcriptionally silent and hidden from the host’s immune defense mechanisms in latent reservoir cells. These latent reservoirs are highly heterogeneous, long-lived cells that are capable of reactivating to restore the viremic stage in virally suppressed individuals upon treatment interruption, thus necessitating life-long antiretroviral treatment. Latency reversal has become one of the most explored therapeutic approaches for eliminating HIV reservoirs and effecting HIV cure. Various aspects governing the establishment, maintenance, and reversal of HIV latency continue to be an enigma and warrant further research. Quantifying the size of the latent reservoir pool is also a challenge as these cells are very few in number and cannot be easily differentiated from uninfected cells. This article provides a comprehensive review of the in vitro and in vivo models currently available for studying HIV latency as well as the recently developed molecular tools for detection and quantification of latent viral reservoirs.

The biological characteristics of early transmitted/founder (T/F) variants are crucial factors for viral transmission and constitute key determinants for the development of better therapeutics and vaccine strategies. The present study aimed to generate T/F viruses and to characterize their biological properties. For this purpose, we constructed 18 full-length infectious molecular clones (IMCs) of HIV from recently infected infants. All the clones were characterized genotypically through whole genome sequencing and phenotypically for infectivity, replication kinetics, co-receptor usage, as well as their susceptibility to neutralizing antibodies and entry inhibitors using standard virological assays. Genotypic analysis revealed that all the T/F clones were of non-recombinant subtype C, but some of them harboured the Y181C drug resistance mutation associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of antiretroviral drugs. In vitro studies showed that while all the IMCs were capable of replicating in PBMCs and utilized the CCR5 co-receptor for cellular entry, the drug-resistant variants had significantly lower replicative capacity and per particle infectivity than the drug-sensitive viruses. Both exhibited similar sensitivities to a standard panel of broadly neutralizing monoclonal antibodies and viral entry inhibitors. These findings suggest that despite their diminished replicative fitness, the drug-resistant T/F variants retain transmission fitness and remain susceptible to neutralizing antibody-based interventions and viral entry inhibitors.

Liposomes are micro-vesicles which are made up of natural or synthetic phospholipids. They were described in 1964 by Dr. Alec D. Bangham, initially called “smectic mesophases” and renamed as “liposomes” later. The name is derived from the Greek words lipos (meaning fats), and soma (meaning body) (Daraee et al., 2014). They are said to be amphipathic and lipophilic molecules which are made up of phospholipid bilayer, consisting of a hydrophilic head group and a hydrophobic tail group, and are usually in the range of 0.5–5.0 µm in diameter. As these have some attractive biological properties such as biodegradability, biocompatibility, non-toxicity, and non-immunogenicity, they can be potent drug delivery systems (Sharma and Sharma, 1997).46

The early diagnosis of tuberculosis with novel non-sputum-based biomarkers is of high priority in End TB strategy. MicroRNAs are significant regulators of TB pathogenesis and their differential expression pattern among healthy, latent, and active TB population has revealed their potentiality as biomarkers in recent studies. We performed systematic review and meta-analysis on the role of host miRNAs in TB diagnosis. PubMed, Ovid, and Cochrane databases were searched to retrieve published literature. Relevant studies were screened, and their quality was assessed using STARD guidelines and QUADAS-2 tool. Heterogeneity of studies and overall pooled results of sensitivity, specificity, and DOR were determined by forest plots. Out of 447 studies, 21 were included for qualitative analysis and eight for meta-analysis. Among these, miR-31 had the maximum diagnostic accuracy, with a sensitivity of 96% (89·7-98·5), specificity of 89% (81·2-93·8), and DOR of 345·9 (90·2-1326·3), meeting the minimal target product profile (TPP) for TB diagnostics. Funding Information: This work was supported by the Department of Science and Technology (DST), DST-INSPIRE fellowship. Declaration of Interests: The authors declare no conflicts of interest.