Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study.

Background: The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the mechanisms remain unclear. The difficulty in elucidating the evolutionary origin of the earliest X4 viruses limits our understanding of this phenomenon.

Methods: We tracked the evolution of the transmitted/founder (T/F) HIV-1 in RV217 participants identified in acute infection.

Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype.

Nearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, detection was not at the earliest stages of acute infection. Here, we identified an X4-tropic T/F HIV-1 in a participant in acute infection cohort.

Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype.

Nearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, detection was not at the earliest stages of acute infection. Here, we identified an X4-tropic T/F HIV-1 in a participant in acute infection cohort.

Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting.

The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the underlying mechanisms remain unclear. The difficulty in capturing the earliest moment of coreceptor switch limits our understanding of this phenomenon. Here, by tracking the evolution of the transmitted/founder (T/F) HIV-1 in a prospective cohort of individuals at risk for HIV-1 infection identified very early in acute infection, we investigated this process with high resolution.

Immune escape mutations selected by neutralizing antibodies in natural HIV-1 infection can alter coreceptor usage repertoire of the transmitted/founder virus.

The ability of HIV-1 to evade neutralizing antibodies (NAbs) in vivo is well demonstrated, but the impact of NAb escape mutations on HIV-1 phenotype other than immune escape itself has rarely been studied. Here, we show that immune escape mutations selected by V3-glycan specific NAbs in vivo can alter coreceptor usage repertoire of the transmitted/founder (T/F) HIV-1. In a participant developed V3-glycan NAb response, naturally selected escape mutations at the V3 N301 and N332 glycan sites abrogated CCR8 usage while conferred APJ usage on the cognate T/F strain.

Distinct mechanisms of long-term virologic control in two HIV-infected individuals after treatment interruption of anti-retroviral therapy.

Certain infected individuals suppress human immunodeficiency virus (HIV) in the absence of anti-retroviral therapy (ART). Elucidating the underlying mechanism(s) is of high interest. Here we present two contrasting case reports of HIV-infected individuals who controlled plasma viremia for extended periods after undergoing analytical treatment interruption (ATI).

Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection in fetuses.

Study of evolution and selection pressure on HIV-1 in fetuses will lead to a better understanding of the role of immune responses in shaping virus evolution and vertical transmission. Detailed genetic analyses of HIV-1 gene from 12 transmission pairs show that most infections (67%) occur within 2 months of childbirth. In addition, the sequences from long-term-infected fetuses are highly divergent and form separate phylogenetic lineages from their cognate maternal viruses.

Emergence of SARS-CoV-2 through recombination and strong purifying selection.

COVID-19 has become a global pandemic caused by the novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis, discovering new drugs, and developing a vaccine. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike and other genes among bat, pangolin, and human coronaviruses, suggesting similar evolutionary constraints in different host species.

Combating a Master Manipulator: Staphylococcus aureus Immunomodulatory Molecules as Targets for Combinatorial Drug Discovery.

Staphylococcus aureus is a bacterial pathogen that can cause significant disease burden and mortality by counteracting host defenses through producing virulence factors to survive the immune responses evoked by infection. This emerging drug-resistant pathogen has led to a decline in the efficacy of traditional antimicrobial therapy. To combat these threats, precision antimicrobial therapeutics have been created to target key virulence determinants of specific pathogens.

Master mechanisms of Staphylococcus aureus: consider its excellent protective mechanisms hindering vaccine development!

Lack of known mechanisms of protection against Staphylococcus aureus in humans represents an important risk factor for skin infections and bacteremia in patients, intern hindering the development of efficacious vaccines. However, development of effective humoral response may be dampened by converging immune-evasion mechanisms of S. aureus.