Plasma viral load may fail as a marker of infectivity of genital secretions. HAART treatment seems to be more efficacious in suppressing viral shedding at the genital level. The female genital tract represents a distinct compartment for HIV-1 replication/evolution.

Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neurological manifestations both in adults and in children. The primary target for HIV-1 infection in the brain is the microglia, but astrocytes can also be infected. We tested 26 primary HIV-1 isolates for their capacity to infect human fetal astrocytes in culture. Eight of these isolates, independent of their biological phenotype and chemokine receptor usage, were able to infect astrocytes. Although no sustained viral replication could be demonstrated, the virus was recovered by coculture with receptive cells such as macrophages or on stimulation with interleukin-1beta. To gain knowledge into the molecular events that regulate attachment and penetration of HIV-1 in astrocytes, we investigated the expression of several chemokine receptors. Fluorocytometry and calcium-mobilization assay did not provide evidence of expression of any of the major HIV-1 coreceptors, including CXCR4, CCR5, CCR3, and CCR2b, as well as the CD4 molecule on the cell surface of human fetal astrocytes. However, mRNA transcripts for CXCR4, CCR5, Bonzo/STRL33/TYMSTR, and APJ were detected by RT-PCR. Furthermore, infection of astrocytes by HIV-1 isolates with different chemokine receptor usage was not inhibited by the chemokines SDF-1beta, RANTES, MIP-1beta, or MCP-1 or by antibodies directed against the third variable region or the CD4 binding site of gp120. These data show that astrocytes can be infected by primary HIV-1 isolates via a mechanism independent of CD4 or major chemokine receptors. Furthermore, astrocytes are potential carriers of latent HIV-1 and on activation may be implicated in spreading the infection to other neighbouring cells, such as microglia or macrophages.

Here we present results from a survey on anti‐SARS‐CoV‐2 seroprevalence in healthy blood donors from a low incidence COVID‐19 area (Apulia region, South Eastern Italy). Among 904 subjects tested, only in 9 cases (0.99%) antibodies against SARS‐CoV‐2 were demonstrated. All the 9 seropositive patients were negative for the research of viral RNA by RT‐PCR in nasopharyngeal swabs. These data, along with those recently reported from other countries, clearly show that we are very far from herd immunity and that the containment measures are at the moment the only realistic instrument we have to slow the spread of the pandemic. This article is protected by copyright. All rights reserved.

Our results demonstrate a correlation between high levels of HIV RNA in CSF and the presence of neurological disorders thus indicating a possible role for HIV-1 RNA in the CSF as a biological marker of neurological disease. The finding of viruses with a different phenotype in paired CSF and PBMC indicates that HIV-1 may evolve differently in the brain and in the blood. This suggests compartmentalization of HIV-1 within the CNS.

Simian virus 40 (SV40) large T antigen (LT) coding sequences were revealed in different human samples, whereas SV40 antibodies (Ab) were detected in human sera of cancer patients and healthy individuals, although with a lower prevalence. Previous studies carried out by the neutralization assay gave a SV40 seroprevalence, in the general population, up to 8%, although higher rates, 12%, were detected in kidney transplant children, in a group of HIV-positive patients, and in healthy females. In this study, serum samples from pregnant women, together with those from non-pregnant women, were analyzed to check the prevalence of IgG Ab reacting to SV40 LT antigens. Serum samples were collected from pregnant and non-pregnant women, with the same mean age. Women were in the range of 15–48 years old. Samples were assayed by an indirect ELISA employing specific SV40 LT mimotopes as antigens, whereas functional analysis was performed by neutralization of the viral infectivity in cell cultures. As a control, sera were analyzed for Ab against BK polyomavirus (BKPyV), which is a human polyomavirus homologous to SV40. Statistical analyses employed chi-square with Yates’ correction, and Student’s t tests. Indirect ELISAs indicated that pregnant women tested SV40 LT-positive with a prevalence of 17% (23/134), whereas non-pregnant women had a prevalence of 20% (36/180) (P > 0.05). Ab against BKPyV were detected with a prevalence of 80% in pregnant women and with a prevalence of 78% in non-pregnant women. These data indicate that SV40 infects at a low prevalence pregnant women. We may speculate that SV40, or a close human polyomavirus still undetected, could be transmitted from mother to fetus.

Although evidence for human immunodeficiency virus 1 (HIV‐1) presence in the central nervous system (CNS) of infected patients is well established, the intensity of viral replication within the brain is not usually known. In vitro, human embryonic microglial cells internalized HIV‐1 through a CD4‐dependent pathway but were not permissive to viral replication. We observed that HIV replication was induced when CNS cell cultures were stimulated for 14 days by a combination of proinflammatory cytokines including IFNγ, IL1β, and TNFα. After long‐term cytokine stimulation, morphologically differentiated glial cells appeared, in which HIV‐1 tat antigen was detected after infection. Thus, variations in the stage of maturation/activation of CNS cells under inflammatory conditions probably play a major role in facilitating massive production of HIV‐1. We then studied the effect of prolonged cytokine stimulation on the secretion of inflammatory mediators by glial cells. An early increased secretion of prostaglandin F2α and chemokines (RANTES>>MIP‐1α>>MIP‐1β) was observed, due to both microglia and astrocytes. In contrast to persistent PGF2α production, an extinction of RANTES and MIP‐1β but not of MIP‐1α secretion occurred during the 14 days of stimulation and was inversely correlated with the ability of glial cells to replicate HIV‐1. The study of the secretory factors produced in response to a persistent inflammation could provide a better understanding of the modulation of HIV replication in glial cells. GLIA 23:304–315, 1998. © 1998 Wiley‐Liss, Inc.

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The most frequent neurological complication of AIDS is a dementia-like syndrome. Power and collaborators (J Virol 1994; 68:4643-4649) have reported an association between the clinical signs of AIDS dementia and the amino acid composition of two positions (305 and 329) within the V3 region of HIV-1 strains amplified from brain tissue. Similarly, we analyzed position 305 in the V3 region of HIV-1 present in the brain or cerebrospinal fluid of 25 nondemented subjects at different clinical stages of HIV-1 infection. Our results are, however, at variance with the findings presented by Power and colleagues. Histidine, found to be common among sequences derived from demented patients, was also present in the majority (16 of 25) of nondemented patients analyzed by us. In the hands of Power and colleagues, sequences derived from nondemented patients contained proline at position 305. None of our patients had proline in this position. We also asked the question whether the presence of a specific amino acid at position 305 of the V3 loop is linked to an increased capacity of HIV-1 isolates to infect primary microglial cells, the major target cell for HIV-1 infection in the brain. Primary HIV-1 isolates derived from blood and cerebrospinal fluid of five patients, two asymptomatic and three AIDS patients, were used to infect microglia cell cultures. Infection was monitored by syncytium formation and by p24 antigen release in the culture supernatant. All but one of the paired blood/CSF isolates replicated in human brain cultures. Replication occurred independently from the amino acid present at position 305 of the V3 region of the viral envelope. Our results indicate that the majority of HIV-1 isolates, even derived during the asymptomatic stage, have the capacity to infect microglial cells. The relevance of viral envelope sequences in determining tropism for microglial cells and development of neurological symptoms remains an open question.