Retroviruses have evolved effective strategies to evade the host immune response, such as high variability and latent infection. In addition, primate lentiviruses, such as HIV-1, have acquired ...several "accessory" genes that antagonize antiviral host restriction factors and facilitate viral immune evasion, thereby allowing continuous and efficient viral replication despite apparently strong innate and acquired immune responses. Here, I summarize some of our current knowledge on the acquisition and function of the viral vif, vpr, vpu, and nef genes, with a particular focus on the evolution and specific properties of pandemic HIV-1 strains that may contribute to their efficient spread and high virulence.
Monkeypox: A New Threat? Kmiec, Dorota; Kirchhoff, Frank
International journal of molecular sciences,
07/2022, Letnik:
23, Številka:
14
Journal Article
Recenzirano
Odprti dostop
The global vaccination programme against smallpox led to its successful eradication and averted millions of deaths. Monkeypox virus (MPXV) is a close relative of the Variola (smallpox) virus. Due to ...antigenic similarity, smallpox vaccines cross-protect against MPXV. However, over 70% of people living today were never vaccinated against smallpox. Symptoms of monkeypox (MPX) include fever, head- and muscle ache, lymphadenopathy and a characteristic rash that develops into papules, vesicles and pustules which eventually scab over and heal. MPX is less often fatal (case fatality rates range from <1% to up to 11%) than smallpox (up to 30%). MPXV is endemic in sub-Saharan Africa, infecting wild animals and causing zoonotic outbreaks. Exotic animal trade and international travel, combined with the increasing susceptibility of the human population due to halted vaccination, facilitated the spread of MPXV to new areas. The ongoing outbreak, with >10,000 cases in >50 countries between May and July 2022, shows that MPXV can significantly spread between people and may thus become a serious threat to public health with global consequences. Here, we summarize the current knowledge about this re-emerging virus, discuss available strategies to limit its spread and pathogenicity and evaluate its risk to the human population.
HIV, the causative agent of AIDS, has a complex evolutionary history involving several cross-species transmissions and recombination events as well as changes in the repertoire and function of its ...accessory genes. Understanding these events and the adaptations to new host species provides key insights into innate defense mechanisms, viral dependencies on cellular factors, and prerequisites for the emergence of the AIDS pandemic. In addition, understanding the factors and adaptations required for the spread of HIV in the human population helps to better assess the risk of future lentiviral zoonoses and provides clues to how improved control of viral replication can be achieved. Here, we summarize our current knowledge on viral features and adaptations preceding the AIDS pandemic. We aim at providing a viral point of view, focusing on known key hurdles of each cross-species transmission and the mechanisms that HIV and its simian precursors evolved to overcome them.
Simian immunodeficiency viruses crossed the barrier from great apes and monkeys to humans on at least 13 occasions, but only a single transmission is responsible for the AIDS pandemic. Sauter and Kirchhoff summarize the cross-species transmission events and adaptations allowing pandemic HIV-1 strains to spread efficiently in the human population.
Any pathologic event in the brain leads to the activation of microglia, the immunocompetent cells of the central nervous system. In recent decades diverse molecular pathways have been identified by ...which microglial activation is controlled and by which the activated microglia affects neurons. In the normal brain microglia were considered “resting,” but it has recently become evident that they constantly scan the brain environment and contact synapses. Activated microglia can remove damaged cells as well as dysfunctional synapses, a process termed “synaptic stripping.” Here we summarize evidence that molecular pathways characterized in pathology are also utilized by microglia in the normal and developing brain to influence synaptic development and connectivity, and therefore should become targets of future research. Microglial dysfunction results in behavioral deficits, indicating that microglia are essential for proper brain function. This defines a new role for microglia beyond being a mere pathologic sensor.
Microglia have been thought to be “resting” in the normal brain but recent data suggest that they play a more active role. Here, Kettenmann et al. summarize evidence that microglia also use the molecular pathways involved in pathology to influence synaptic development and connectivity in the normal brain.
In the subset of primate lentiviruses that contain a vpu gene - HIV-1 and its simian precursors - the Nef protein has lost the ability to down-modulate CD3, block T cell activation and suppress ...programmed death. Vpu counteracts a host restriction factor induced by the inflammatory cytokine interferon-alpha. I propose that the acquisition of vpu may have allowed the viral lineage that gave rise to HIV-1 to evolve towards greater pathogenicity by removing the selective pressure for a protective Nef function that prevents damagingly high levels of immune activation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neuronal N-methyl-D-aspartate (NMDA) receptors are well known for their pivotal role in memory formation. Originally, they were thought to be exclusive to neurons. However, numerous studies revealed ...their functional expression also on various types of glial cells in the nervous system. Here, the methodology how to study the physiology of NMDA receptors selectively on astrocytes will be described in detail. Astrocytes are the main class of neuroglia that control transmitter and ion homeostasis, which link cerebral blood flow and neuronal energy demands, but also affect synaptic transmission directly.
Detection of SARS-CoV-2 in human breastmilk Groß, Rüdiger; Conzelmann, Carina; Müller, Janis A ...
The Lancet (British edition),
06/2020, Letnik:
395, Številka:
10239
Journal Article
TMPRSS2 is a type II transmembrane protease with broad expression in epithelial cells of the respiratory and gastrointestinal tract, the prostate, and other organs. Although the physiological role of ...TMPRSS2 remains largely elusive, several endogenous substrates have been identified. TMPRSS2 serves as a major cofactor in SARS-CoV-2 entry, and primes glycoproteins of other respiratory viruses as well. Consequently, inhibiting TMPRSS2 activity is a promising strategy to block viral infection. In this review, we provide an overview of the role of TMPRSS2 in the entry processes of different respiratory viruses. We then review the different classes of TMPRSS2 inhibitors and their clinical development, with a focus on COVID-19 treatment.
Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and ...their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.
Viruses may not only affect our daily lives but also shape our genome evolution. A recent study shows that the zinc-finger antiviral protein (ZAP) drives CpG suppression in a biased manner. Genes ...involved in the defense against viral invaders are particularly CpG suppressed to avoid self-targeting and to promote an effective immune response.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
