Infectious Virus In Blood Research Articles

Risk of transmission of severe acute respiratory syndrome coronavirus 2 by transfusion: A literature review.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a novel human coronavirus responsible for coronavirus disease 2019 (COVID‐19). The emergence of this virus in Wuhan, China, at the end of 2019 and its worldwide spread to reach the pandemic stage has raised concerns about the possible risk that it might be transmissible by transfusion. This theoretical risk is further supported by reports of the detection of viral RNA in the blood of some infected individuals. To further address this risk, a thorough PubMed literature search was performed to systematically identify studies reporting data on the detection of SARS‐CoV‐2 RNA in blood or its components. Complementary searches were done to identify articles reporting data on the in vitro infectivity of blood components. At least 23 articles presenting data on the detection of SARS‐CoV‐2 RNA in blood, plasma, or serum were identified. Of these, three studies reported on blood donors with COVID‐19 infection identified after donation, and no cases of transfusion transmission were identified. A few studies mentioned results of in vitro infectivity assays of blood components in permissive cell lines, none of which were able to detect infectious virus in blood or its components. Complementary searches have identified reports demonstrating that the correlation between the presence of viral RNA in a biologic sample and infectivity requires a minimal RNA load, which is rarely, if ever, observed in blood components. Overall, the available evidence suggests that the risk of transmission of SARS‐CoV‐2 by transfusion remains theoretical.

Blood CXCR3+ CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals

We recently demonstrated that lymph nodes (LNs) PD-1+/T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals. In the present study, we show that blood CXCR3-expressing memory CD4 T cells are enriched in cells containing inducible replication competent virus and contributed the most to the total pool of cells containing replication competent and infectious virus in blood. Interestingly, subsequent proviral sequence analysis did not indicate virus compartmentalization between blood and LN CD4 T-cell populations, suggesting dynamic interchanges between the two compartments. We then investigated whether the composition of blood HIV reservoir may reflect the polarization of LN CD4 T cells at the time of reservoir seeding and showed that LN PD-1+ CD4 T cells of viremic untreated HIV-infected individuals expressed significantly higher levels of CXCR3 as compared to CCR4 and/or CCR6, suggesting that blood CXCR3-expressing CD4 T cells may originate from LN PD-1+ CD4 T cells. Taken together, these results indicate that blood CXCR3-expressing CD4 T cells represent the major blood compartment containing inducible replication competent virus in treated aviremic HIV-infected individuals.

Detection of MLV-like gag sequences in blood samples from a New York state CFS cohort

A blinded study was undertaken to determine whether XMRV or MLV-like virus could be detected in peripheral blood from 40 adult subjects divided into three groups: severely ill with CFS, recovered from CFS, and a control group lacking a CFS diagnosis at any time. All patients in the“severe CFS” group currently meet Fukuda criteria. “Recovered CFS” subjects had scores on the SF-36 survey instrument that were significantly lower than the healthy control group, according to Hotelling’s T2 test. Blood was collected in EDTA tubes and cDNA and DNA made from PBMCs. Plasma was incubated with LNCaP cells that were subsequently passaged. Nested PCR with USB Hot-Start IT FideliTaq was performed with gag primers. Any PCR products of expected sizes were sequenced. Samples were tested for mouse contamination with primers to IAP and/or mouse mitochondrial DNA. gag sequences were detected in both severe and recovered CFS subjects’ blood as well as in some healthy controls. gag sequences could be amplified from genomic DNA from LNCaP cells of some subjects after 4 or 6 subcultures following incubation with certain subjects’ plasma, indicating the presence of infectious virus in blood. All gag sequences detected in this cohort were more similar to the MLV-like sequences reported by Lo et al. (2010) than to the XMRV sequences reported by Lombardi et al. (2009). Detection of gag sequences in whole blood genomic DNAs that were negative for mouse IAP and mitochondrial DNA provides strong evidence for infection of humans with MLV-like viruses.

The transmission of Jembrana disease, a lentivirus disease of Bos javanicus cattle.

Methods of transmission of Jembrana disease, an acute and severe disease of Bali cattle (Bos javanicus) caused by a recently-identified bovine lentivirus known as Jembrana disease virus, are described. During the acute disease virus can be detected in saliva and milk. There is evidence of direct transmission from acutely affected animals in close contact with susceptible cattle, possibly by virus in these secretions infecting cattle by the conjunctival, intranasal or oral routes, by which it was possible to infect cattle experimentally. During the acute disease the titre of infectious virus in blood is high, about 10(8) 50% cattle infectious units (ID50)/ml, and it is probable that the virus is also transmitted mechanically by haematophagous arthropods. Recovered cattle are also a potential but probably infrequent source of infection; recovered cattle are persistently viraemic but the titre of infectious virus in blood decreases to about 10(1) ID50/ml by 60 days after recovery from the acute disease, and virus cannot be detected in secretions.

Mechanisms of HIV/SIV mucosal transmission.

The Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), organized a Workshop on HIV/SIV Pathogenesis and Mucosal Transmission on March 14-17, 1994, attended by over 300 participants. The purpose of the workshop was to foster research in the areas of HIV pathogenesis, mucosal transmission, and host factors modulating HIV infection and disease. This article summarizes workshop presentations that focused on mechanisms of HIV or SIV mucosal transmission. The following are highlights from the workshop. The epidemiological data indicating a low probability of infection from a single sexual exposure are consistent with observations that infectious cell-free or cell-associated HIV could be isolated from only 10-57% of semen samples, and that high levels of SIV are required for infection by a mucosal route. Several lines of circumstantial evidence suggest that an important property of a transmitted HIV or SIV is the ability to infect macrophages. A potential mechanism for cell-associated mucosal transmission is provided by the observations that CD4-negative epithelial cells in culture are efficiently infected by direct contact with HIV-infected T cells, and that HIV-infected epithelial cells are observed in vivo. Cell-free HIV virions contain partial reverse transcripts of viral RNA into DNA, and conditions that promote DNA reverse transcripts, such as incubation in seminal fluid, increase viral infectivity. Finally, evidence is accumulating that transient or abortive infection with short-term recovery of infectious virus in blood can occur in the absence of seroconversion.

Immune activation and viral burden in acute disease induced by simian immunodeficiency virus SIVsmmPBj14: correlation between in vitro and in vivo events

The simian immunodeficiency virus SIVsmmPBj14 (SIV-PBj14) is an atypical lentivirus that causes acute disease and death in pig-tailed macaques and in vitro replicates efficiently in resting macaque lymphocytes and activates and induces proliferation of lymphocytes. The present study was conducted to test the hypothesis that production of large quantities of SIV-PBj14 induces widespread immune activation and elaboration of cytokines which lead directly to the death of infected pig-tailed macaques. Following intravenous inoculation of pig-tailed macaques with SIV-PBj14, acute disease developed and was characterized by high levels of plasma viremia, p27gag antigenemia, tumor necrosis factor alpha, and interleukin-6 (IL-6). All animals died within 10 days of infection, at which time some animals had as many as 100% CD4+ cells in the periphery and lymphoid tissues infected. During the last few days before death, titers of infectious virus in blood increased as much as 10(5)-fold. By using dual-label immunofluorescence assays for detection of cell surface activation markers, both CD4+ and CD8+ lymphocytes were shown to express the IL-2 and transferrin receptors following either in vivo or in vitro infection with SIV-PBj14. Furthermore, in vitro infection of quiescent macaque lymphocytes by SIV-PBj14 was accompanied by proliferation of both CD4+ and CD8+ lymphocyte subsets, as measured by incorporation of [3H]thymidine. Increases in numbers of activated lymphocytes and levels of proinflammatory cytokines in plasma coincided with increased amounts of detectable virus in vivo. Clinical signs of disease and pathologic findings were most consistent with death from a shock-like syndrome, in which acute-phase inflammatory cytokines are known to play a major role. Tumor necrosis factor alpha, IL-2, and IL-6 were detected in some cultures infected with SIV-PBj14, but this finding was not consistent. When cytokines were detected, their concentrations were essentially no different from those found in control cultures infected with SIVsmm9, a prototypic strain from which SIV-PBj14 was derived. The in vivo results suggest a synergistic cycle of activation of lymphocytes and monocytes, elaboration of cytokines, and virus production that accelerates uncontrolled and culminates in death. The observed correlations between in vivo and in vitro activation events following SIV-PBj14 infection validate the use of in vitro studies to clarify lentivirus-lymphocyte interactions that may contribute to the virulence of SIV-PBj14.