A rapidly expanding pandemic In early December 2019, several local health facilities first reported pneumonia cases of unknown origin in Wuhan, China. This new coronavirus infectious disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 1, 2020 and identified as a previously unknown betacoronavirus (1, 2). Since then, studies have increasingly demonstrated that SARS-CoV-2 can be transmitted effectively among humans through aerosol or fomites (3-5). With transmission capabilities even before symptom onset (6, 7), this pandemic is rapidly evolving and expanding. As of April 2, 2020, a total of 962,977 confirmed cases of COVID-19 and 49,180 deaths have been reported across 180 countries and regions. Recent models indicated that as much as 86% of all infections early in the spread were undocumented, suggesting the real number of infections is likely much greater (8). As a public health emergency of international concern, COVID-19 was declared a pandemic by the World Health Organization. Public health authorities around the globe are now racing to contain the spread.

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There is intense interest in developing curative interventions for HIV. How such a cure will be quantified and defined is not known. We applied a series of measurements of HIV persistence to the study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor. Samples from blood, spinal fluid, lymph node, and gut were analyzed in multiple laboratories using different approaches. No HIV DNA or RNA was detected in peripheral blood mononuclear cells (PBMC), spinal fluid, lymph node, or terminal ileum, and no replication-competent virus could be cultured from PBMCs. However, HIV RNA was detected in plasma (2 laboratories) and HIV DNA was detected in the rectum (1 laboratory) at levels considerably lower than those expected in ART-suppressed patients. It was not possible to obtain sequence data from plasma or gut, while an X4 sequence from PBMC did not match the pre-transplant sequence. HIV antibody levels were readily detectable but declined over time; T cell responses were largely absent. The occasional, low-level PCR signals raise the possibility that some HIV nucleic acid might persist, although they could also be false positives. Since HIV levels in well-treated individuals are near the limits of detection of current assays, more sensitive assays need to be developed and validated. The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure.

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Highlights d Defective viral genomes predominate in treated SIV mac and HIV-2 infection d Significantly more SIV proviruses are intact compared to HIV-1 in treated humans d Compared to HIV, clonal sequences and deleted genomes are less frequent in SIV infection d An assay to directly enumerate intact SIV genomes was developed

We isolated a Vibrio vulnificus mutant that was deficient in both metalloprotease and cytolysin by allelic exchange. The virulence of this mutant in mice and its cytotoxicity for HEp-2 cells were comparable to those of the wild-type strain, indicating that neither factor was essential for these properties. The cytolysin, but not the protease, seemed to be important for causing damage in the alimentary tract of the mice.Vibrio vulnificus, a gram-negative estuarine bacterium, causes wound infections and septicemia in humans, mostly in immunocompromised people and those with underlying conditions such as hemochromatosis, liver cirrhosis, and alcoholism (2,3,5,23). Infection is usually acquired via direct contact or the gastrointestinal (GI) route; in both cases, skin lesions with ulcer and edema are common (5,12,32).Strains of V. vulnificus secrete a variety of products that have been implicated in bacterial virulence and pathogenesis, including capsular polysaccharide (34), cytolysin (7, 16), metalloprotease (protease) (15,19), phospholipases (31), and siderophores (25). The purified protease of V. vulnificus has been shown to increase vascular permeability and induce edema by activating the plasma kallikrein-kinin cascade (18,21,22) and to cause hypodermic hemorrhage (20). It also facilitates bacterial acquisition of iron by digesting heme proteins, transferrin and lactoferrin (24). The cytolysin, a pore-forming cytotoxin and hemolysin (13), is lethal to mice at a submicrogram level (26). It damages mast cells, resulting in release of histamine (36), and causes hypotension, tachycardia (14), and skin (9) and pulmonary (26) damage in animals. Collectively, the cytolysin and the protease are thought to be important for the pathogenesis of V. vulnificus. The presence of cytolysin in V. vulnificus-infected mice (10) and the detection of anticytolysin antibodies in sera from mice and a human that survived V. vulnificus disease (8) further support the role of cytolysin in disease development.Genes encoding the protease (4) and cytolysin (35) of V. vulnificus have been cloned, and isogenic mutants deficient in either gene product have been isolated by an allelic exchange technique (29, 33). Although purified cytolysin and protease exhibited a variety of biological activities that seemed to be detrimental to the animals, elimination of either factor did not attenuate the pathogenicity in mice, as assayed with several animal models (29,33). In fact, the protease-deficient (PD) mutant was even more virulent than the wild-type strain in mice challenged orally (29). As mentioned above, both the cytolysin and the protease are able to increase vascular permeability and cause tissue damage, which may enhance bacterial invasiveness. Therefore, deficiency in either factor may not be sufficient to reduce the bacterial virulence, since compensation of the other factor may occur. We therefore reasoned that elimination of both factors may be necessary for attenuation of bacterial virulence. To test this hypothesis, we generated a dou...

Despite antiretroviral therapy (ART) which halts HIV-1 replication and reduces plasma viral load to clinically undetectable levels, viral rebound inevitably occurs once ART is interrupted. HIV-1-infected cells can undergo clonal expansion, and these clonally expanded cells increase over time. Over 50% of latent reservoirs are maintained through clonal expansion. The clonally expanding HIV-1-infected cells, both in the blood and in the lymphoid tissues, contribute to viral rebound. The major drivers of clonal expansion of HIV-1-infected cells include antigendriven proliferation, homeostatic proliferation and HIV-1 integration site-dependent proliferation. Here, we reviewed how viral, immunologic and genomic factors contribute to clonal expansion of HIV-1-infected cells, and how clonal expansion shapes the HIV-1 latent reservoir. Antigen-specific CD4 + T cells specific for different pathogens have different clonal expansion dynamics, depending on antigen exposure, cytokine profiles and exhaustion phenotypes. Homeostatic proliferation replenishes the HIV-1 latent reservoir without inducing viral expression and immune clearance. Integration site-dependent proliferation, a mechanism also deployed by other retroviruses, leads to slow but steady increase of HIV-1-infected cells harboring HIV-1 proviruses integrated in the same orientation at specific sites of certain cancer-related genes. Targeting clonally expanding HIV-1 latent reservoir without disrupting CD4 + T cell function is a top priority for HIV-1 eradication.