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Microbes & Immunity RANTES/CCL5 and ezrin peptide RepG3 for long COVID

3.6. RANTES/CCL5 and influenza A infection Persistent infection of basal keratinocytes with HPV-16 or

RANTES/CCL5 expression amplifies T-cell immunity HPV-18 is likely to induce cancer.
and inhibits the replication of influenza A virus. This These cancer-causing hrHPVs have evolved
upregulation of RANTES/CCL5 is dependent on PKC mechanisms to evade both innate and adaptive immune
activation. RANTES/CCL5 also induces the upregulation defenses. Innate immune defenses by pattern recognition
of “SAM domain and HD domain-containing protein 1” receptors (PRRs) are compromised by hrHPV proteins
(SAMHD1), an antiviral restriction factor for influenza A. 36 blocking TLR signaling through TRAF3 > TANK-binding
kinase downstream to NF-κB and proinflammatory
3.7. RANTES/CCL5 and dengue virus infection cytokine expression in the nucleus. Programmed adaptive
Mosquitos are vectors for dengue virus (DENV) infection, immune defenses are also compromised by hrHPV, which
which causes hemorrhagic fever, which is a major inhibits RANTES/CCL5 expression and secretion, leading
world health problem in the tropics. It is estimated that to weak T-cell help, compromised B-cell mediated antibody
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390 million dengue infections occur each year, of which production, and poor CD8 CTL responses.
96 million manifest as hemorrhagic fever. High levels of
RANTES/CCL5 expression prevent the development of 3.10. RANTES/CCL5 and LCMV infection
severe dengue fever by amplification of T-cell immunity LCMV is a prevalent human viral pathogen that infects
and inhibition of the virus life cycle. Dengue virus uses 2%–5% of the population of the US and Europe and causes
the CCR5 receptor, which is blocked by high levels of substantial neurological problems, including meningitis.
RANTES/CCL5, to directly inhibit DENV infection. RANTES/CCL5 is vital for the control of systemic LCMV
37
Increased hepatic RANTES/CCL5 levels in the liver protect infection in humans to prevent acute LCMV infection
patients with acute dengue from liver damage and elevated from becoming chronic. Serum levels of RANTES/CCL5
serum transaminase levels. 38 are higher in patients with chronic LCMV infection than
in patients with acute LCMV infection.
3.8. RANTES/CCL5 and herpes virus sexual infections
During the acute LCMV infection phase, macrophages
According to the WHO, about 3.7 billion people under are one of the main cell types infected by LCMV, which is
the age of 50 have herpes simplex virus type 1 (HSV-1) a pre-emptive strike by the virus on the immune defense
infection, the main cause of oral herpes. An estimated against LCMV. During chronic LCMV infection, CD8
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490 million people aged 15–49 years worldwide have T-cells become exhausted and dysfunctional. CD8 T-cells
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herpes simplex virus Type 2 (HSV-2) infection, the main lose their capacity for cytokine production and cytotoxicity
cause of sexually transmitted genital herpes infections. while inhibitory receptor expression increases, hindering
Herpes simplex virus infection leads to chronic disease the ability to control LCMV infection.
and regular acute outbreaks. In chronically infected HSV
patients, the virus lies dormant in the infected trigeminal In the mouse infection model of LCMV, RANTES/
ganglia. RANTES/CCL5 is upregulated to maintain CCL5-producing CD4 T-cells are essential to control
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memory T lymphocytes near neurons and can prevent viremia, which can persist for 2–3 months. In contrast, if
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the reactivation of HSV and herpetic lesions. HSV-1 and CD4 T-cells are transiently depleted at the time of infection
39
HSV-2 are neurotropic viruses that can cause encephalitis by LCMV, the mice become viremic for life. In mice lacking
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in newborns and immunocompromised people. RANTES/ CD4 T-cells producing RANTES/CCL5, LCMV viral
CCL5 expression is increased during herpetic encephalitis titers are much higher. In null-RANTES/CCL5 mutant
and amplifies T-cell recruitment to the central nervous mice, CD4 T-cell help is non-functional, resulting in a
+
system. 40 substantial reduction in the cytotoxic potential of virus-
specific CD8 T-cells against LMCV infection. Mice lacking
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3.9. RANTES/CCL5 and HPV sexual infections RANTES/CCL5 signaling have reduced virus-specific CD8
+
+
Human papillomavirus (HPV) is a sexually transmitted T-cell numbers, severe CD8 T-cell exhaustion, reduced
small double-stranded DNA virus that infects production of cytokines, higher expression of inhibitory
undifferentiated keratinocytes of the squamous epithelia of receptors, and higher LCMV viral loads. 23
the anogenital and head and neck regions. The prevalence 3.11. RANTES/CCL5 and other virus infections
41
of HPV is approximately 31% of the global population,
and 21% of the global population carries high-risk HPV High levels of RANTES/CCL5 expression are vital for
(hrHPV) variant genotypes that induce cervical and defense against flaviviruses such as WNV and yellow fever
other cancers. The most prevalent cancer-causing hrHPV virus (YFV). The YFV is the causative agent of hemorrhagic
genotype is HPV-16, which infects 5% of the population. fever that causes severe liver injury and jaundice, hence the

Volume 1 Issue 1 (2024) 6 doi: 10.36922/mi.2474